RSC Advances
REVIEW
Cite this: RSC Adv., 2015, 5, 43242
The chemistry and bioactivity of Southern African
flora I: a bioactivity versus ethnobotanical survey of
alkaloid and terpenoid classes
Smith B. Babiaka,†ab Fidele Ntie-Kang,†‡*ab Lydia L. Lifongo,ab Bakoh Ndingkokhar,ab
James A. Mbah*b and Joseph N. Yong*b
As a whole, the African continent is highly endowed with a huge floral biodiversity. Natural products which
have been isolated from plants growing in this region have shown interesting chemical structures with
Received 30th January 2015
Accepted 13th April 2015
diverse biological activities, which could serve as a starting point for drug discovery. In this study, a
literature survey led to the collection of 864 secondary metabolites from 101 plant species from 57 plant
families. A correlation between the known biological activities of isolated compounds and the
ethnobotanical uses of the plants has been attempted. This review is a survey of the bioactivities of
DOI: 10.1039/c5ra01912e
alkaloids and terpenoids which have been isolated from Southern African flora versus the ethnobotanical
www.rsc.org/advances
uses of the plants used in Southern African traditional medicine.
1
Department of Chemistry, Chemical and Bioactivity Information Centre, Faculty of
Science, University of Buea, P.O. Box 63, Buea, Cameroon. E-mail: ntiekdele@
gmail.com; dele.ntie-kang@ubuea.cm; Tel: +237 677915473
Introduction
a
Department of Chemistry, Faculty of Science, University of Buea, P.O. Box 63, Buea,
Cameroon. E-mail: ajeck.james@ubuea.cm; joseph.yong@ubuea.cm; Tel: +237 677
30 67 42; +237 677 53 73 80
b
† These authors contributed equally.
‡ Present
address:
Department
of
Pharmaceutical
Chemistry,
Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120
Halle (Saale), Germany.
Smith Babiaka studied Chemistry at the University of Buea,
Cameroon, where he subsequently obtained his Bachelor of
Science degree in 2005 and his
Master of Science degree in
2011. Since 2012 he has been
enrolled for a PhD in Chemistry
at the same university working
on natural products/organic
synthesis. His previous work
has been focused on the extraction, purication and characterisation of natural products from African medicinal plants. His
current assignment at the Chemical and Bioactivity Information
Centre consists in developing natural product databases for
African medicinal plants and knowledge bases for environmentally
harmful chemicals.
43242 | RSC Adv., 2015, 5, 43242–43267
The African continent is highly endowed with a huge oral
biodiversity and its plant material contains natural products
(NPs) with interesting chemical structures with diverse biological activities, which could serve as a starting point for drug
discovery programs.1,2 Moreover, medicinal plants from Africa
have played an important socio-economic role by fullling
health-care needs and creating business opportunities for the
Fidele Ntie Kang studied Chemistry at the University of Douala
in Cameroon between 1999 and
2004, leading to BSc and MSc
degrees. His PhD work at the
Centre for Atomic Molecular
Physics and Quantum Optics
(CEPAMOQ) was based on
computer-aided design of antitubercular agents. He has experience in molecular modeling
and has been involved in the
design and management of 3D
structural databases of natural products from African ora for
virtual screening. Fidele currently works as a Research Scientist/
Senior Instructor at the Chemical and Bioactivity Information
Centre (CBIC), hosted at the Chemistry Department of the
University of Buea, Cameroon. He is currently a Georg Forster
postdoctoral fellow, funded by the Alexander von Humboldt
Foundation, Germany.
This journal is © The Royal Society of Chemistry 2015
Review
RSC Advances
less privileged population of the developing world.3 In the past
centuries, a majority of the local population, especially south of
the Sahara have depended on medicinal plants as their main
source of treatment of medical disorders and ailments.4 Thus,
several plant species have been used in Africa traditional
medicine (ATM) to treat various diseases/ailments. Traditional
medicine has been dened by the World Health Organization
(WHO) as practices, knowledge and belief systems which use
minerals, plants and animal based remedies, spiritual therapies
and exercises to prevent, treat and maintain well being.5,6
Traditional medical practices are common in Africa, as well as
in most undeveloped nations, in which majority of the (mostly
poor) population rely on traditional medicines for their health
care. In recent years, ATM has gained renewed interest in the
health care services throughout the continent despite the
advances in Western medicine (WM).7
The region of Southern Africa has a rich biological and
ethnic diversity.8 More than three centuries of botanical
research and exploration in South Africa and neighbouring
countries have revealed promising oristic diversity, with
approximately 25 000 plant species and more than 50% endemism in the region.9,10 The cultural value of biodiversity and its
importance in effective biodiversity conservation planning and
ecotourism have also been recognised recently.11 As a result of
the existing account of the importance and uses of ora of
Southern Africa, there is growing need for ethnobotanical
research.
It has been the objective of the Chemical Bioactivity Information Centre to document knowledge from African ora,
relevant for drug discovery programs on the continent. Previous
review papers have been focused on the bioactivity versus
ethnobotanical survey of medicinal plants from Central,
Lydia Lifongo is a lecturer at the
Department
of
Chemistry,
University of Buea, Cameroon.
She is concurrently the Administrative Manager of the Chemical and Bioactivity Information
Centre, hosted at the department. Lydia obtained her BSc in
Chemistry from the University of
Buea, Cameroon in 1996 and
later obtained an MSc in
Chemistry in 1998 at the same
institution before moving to East
Anglia (United Kingdom), where she obtained her PhD in Environmental Science. At the moment, her focus is on the research
activities of the centre, which include developing knowledge bases
for bioactivity data and environmental toxicity.
James Mbah studied chemistry
at the University of Buea in
Cameroon where he obtained
his BSc in Chemistry and later
obtained an MSc in Organic
Chemistry from the University of
Dschang in Cameroon. He
subsequently obtained a PhD in
Organic Chemistry from the
University of Yaoundé I, Cameroon in 2003, under the joint
supervision of Professors Pierre
Tane and Bonaventure Ngadjui.
Both his doctoral and postdoctoral research projects have been
focused on the search for drug leads from Cameroonian medicinal
plants for the treatment of tropical diseases. He is currently a
lecturer/research group leader in Phytochemistry and Head of
Laboratories at the Department of Chemistry, University of Buea,
Cameroon.
Bakoh Ndingkokhar is currently
a trainee in cheminformatics at
the Chemical and Bioactivity
Information Centre (CBIC),
hosted at the Chemistry
Department of the University of
Buea, Cameroon. He was born
in Cameroon on 1987 and
obtained his undergraduate
degree in Chemistry aer
successful studies from 2009 to
2014 at the University of Buea,
Cameroon. His current assignments include outsourcing data from the chemical cosmetics
database and building the natural products database for Southern
African medicinal plants for virtual screening purposes.
Joseph Yong is currently a
lecturer/Head of Department in
the Chemistry Department of the
University of Buea. He obtained
a “Licence en Chimie” from the
University of Yaoundé in 1979
and pursued further studies at
the University of New Orleans
and the University of Rhode
Island, USA where he acquired
MS and PhD degrees in 1986
and 1991, respectively. He started teaching at the University of
Yaoundé in 1992 and moved to the University of Buea in 1998. His
present area of research focuses on the use of ethnomedical
knowledge to look for drug leads from plants and mushrooms in
Cameroon for the remedy of neglected tropical diseases particularly, malaria, tuberculosis and onchocerciasis.
This journal is © The Royal Society of Chemistry 2015
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Western and Northern Africa has been done and published
by this research group,3,7,12,13 including the development of
natural product databases (CamMedNP, ConMedNP, AfroDb,
p-ANAPL)14–17 and the pharmacokinetic proling of natural
products from African ora,17–19 with the view of drug
discovery. Recent review articles have focused on antimalarial and anti-tubercular principles from African
ora,19–21 while also focusing on different countries/regions
in Africa.3,20–22 This has received signicant attention from
the readership involved in drug discovery from medicinal
plants and thus has prompted the need to explore other
regions of the continent, including Southern Africa. To the
best of our knowledge there has not been a recent review
focusing on the phytochemical and bioactivity of natural
products from the Southern Africa region (covering the
countries; Angola, Botswana, Madagascar, Malawi, Mozambique, Namibia, South Africa, Swaziland and Zimbabwe), in
spite of the rich oral biodiversity and phytochemistry of this
region.8 In this review series, the chemistry and biological
activity of Southern Africa ora would be discussed. In the
present paper, our main focus would be on alkaloids and
terpenoids to highlight the medicinal value and potentials of
the isolated phytochemicals by discussing the bioactivity of
the isolated principles versus ethnobotanical uses of the
plant species.
2 Alkaloids from Southern African
flora
In this report, summaries of the most interesting results for
alkaloids which exhibit biological activities correlating with the
ethnobtanical uses of the plant species of origin have been
shown in Table 1 and 2, while the chemical structures of the
isolated compounds are shown in Fig. 1.
Boophone disticha (Amaryllidaceae) is a common bulbous
plant used traditionally by the local populations of Southern
Africa, mostly as a narcotic substance and for the treatment of a
host of ailments, including inammation, wounds, gynaecological conditions and psychosis.23 Cheesman et al. have isolated the crinane alkaloids; buphanidrine (1) and distichamine
(2) from the bulbs of this plant, collected in the Mpophomeni
area of KwaZulu-Natal (South Africa).24 The isolated compounds
were novel, broad spectrum moderately active, antibacterial
agents with the best MIC value detected at 0.063 mg mL 1 for
Staphylococcus aureus, Escherichia coli and Klebsiella pneumonia.24 MIC values for Bacillus subtilis were two-fold less than
those observed for the other three bacteria, suggesting that the
extract and pure compounds were selective in their interaction
with the bacterial pathogens. The close structural similarity of
these two compounds (1 and 2) may have bearing on their
similar activity proles. Moreover, the bioactivities of these
chemical structures of compounds 1 and 2 may be the basis of
the reputed traditional use of the plant for wounds and
infections.24
There are several reports on the ethnomedical use of Tabernaemontana elegans (toad tree) pertaining to antibacterial
43244 | RSC Adv., 2015, 5, 43242–43267
Review
activity, as well as on the screening of the plant extracts.25–31
Some of these reports pertain to the antibacterial activity: a
root decoction is applied as a wash to wounds, and drunk for
pulmonary diseases and chest pains by the VhaVenda25 and
Zulu26 people of South Africa. Other ethnomedical uses of this
plant include the treatment of heart diseases with the seeds,
stem-bark and roots and the root-bark and properties.27
Extracts of this plant has previously demonstrated antibacterial activity against S. aureus and antimycobacterial activity
against M. smegmatis,28 as well as anti-fungal activity against
Candida albicans.30 Extracts from T. elegans, along with those
from seven other species of the genus Tabernaemontana have
shown antibacterial activity against Gram-positive bacteria.31
Pallant et al. have isolated the indole alkaloids; voacangine (3)
and dregamine (4) as the active antibacterial components of
the plant.32 The study conrms both the antibacterial activity of
T. elegans and supports its potential for being investigated
further for the development of a novel antibacterial compound.
Hypophorine (5) is an indole alkaloid isolated from Erythrina
lysistemon, a leguminous plant harvested in Botswana.33 The
extracts from this plant have been used in traditional medicine
and have also shown antiviral, anticancer and cytotoxic activities.34,35 Although erythrinaline alkaloids36,37 and prenylated
avonoids are known to be prevalent in the plant species,33,38
compound 5 is known to contribute to its antimicrobial
activities.33
Spirospermum penduliorum (Menispermaceae) is endemic
in Madagascar.39 Moreover, the decoctions of all parts of this
plant are traditionally used as anticholinergic and vasorelaxant, among other uses.39 Rafamantanana et al. have isolated two aporphine alkaloids; neolitsine (6) and dicentrine (7)
from the leaves of this plant.40 Both dicentrine and neolitsine
are known to possess antihypertensive activities, dicentrine
having an EC50 value of 0.15 0.04 mg mL 1 on rat aorta
relaxation.40
A review on plants traditionally used for the treatment of
malaria in Madagascar, showed Vepris ampody as a key
component in anti-malarial preparations in Madagascan traditional medicine.41 In Kenya, a decoction of the roots of Vepris
glomerata is used traditionally in the treatment of malaria, while
the vapour is used to treat eye problems. A decoction of the bark
is used in the treatment of cardiac pain while epilepsy, stroke
and psychosis is treated using an aqueous root extract of the
plant mixed with tea.42,43 The furoquinoline alkaloids; indersiamine (8) and maculosidine (9) have been isolated from the
sister species Vepris uguenensis, harvested in Kenya.44
Compounds 8 and 9 were tested against 3D7 (chloroquine
susceptible, CQS) and FCM29 (chloroquine resistant, CQR)
strains of Plasmodium falciparum. It was found that while
compound 8 was completely inactive against both strains of the
parasite, compound 9 displayed mild activity, with IC50 values
of 13.0 1.5 mg mL 1 and 13.8 1.0 mg mL 1 against the CQS
and CQR strains, respectively.44
The Flaky cherry-orange tree, Teclea gerrardii (Rutaceae),
which occurs in riverine thicket and dry forest along the
eastern seaboard of Southern Africa (South Africa, Swaziland
and Southern Mozambique) has been included in this study.
This journal is © The Royal Society of Chemistry 2015
Review
RSC Advances
Table 1 Summary of the bioactivity of derived alkaloids (crinane, indole, bisindole, aporphine and furoquinoline) versus ethnobotanical uses of
plant species
Compound
subclass
Isolated metabolites
Plant species
(country)
Crinane
alkaloids
Buphanidrine (1) and
distichamine (2)
Indole
Family
Ethnobotanical use
Boophone disticha
(South Africa)
Amaryllidaceae
Voacangine (3) and
dregamine (4)
Tabernaemontana
elegans (South
Africa)
Apocynaceae
Hypophorine (5)
Erythrina lysistemon Leguminosae
(Botswana)
Aporphine
Neolitsine (6) and
dicentrine (7)
Spirospermum
penduliorum
(Madagascar)
Menispermaceae
Furoquinoline
Flindersiamine (8) and
maculosidine (9)
Evoxine (10) and 7-(g,gdimethylallyloxy)-gfagarine (11)
Vepris uguenensis
(Kenya)
Teclea gerrardii
(South Africa).
Rutaceae
As an arrow poison
as well as a narcotic;
use decoctions,
extracts and
infusions of bulbs
for numerous
ailments including
treatment of burns,
wounds, pain,
inammation,
anxiety,
gynaecological
conditions and
psychosis23
Applied as a wash to
wounds, and drunk
for pulmonary
diseases and chest
pains, treatment of
heart diseases and
cancer25,26
The extracts from
this plant have been
used in traditional
medicine and have
also shown antiviral,
anticancer and
cytotoxic
activities34,35
Decoction of all
parts is traditionally
used as
anticholinergic and
vasorelaxant and the
decoction of leaves
is also used for the
treatment of malaria
and as a
chloroquine
adjuvant, the
decoction of roots
was taken as
cholagogue, tonic
and for hepatic
disorders39
Treatment of
malaria41
Bark decoctions are
taken for chest
complaints45
Bark decoctions of the plant are employed traditionally by the
Zulus for chest complaints.45 Waffo et al. identied the furoquinoline alkaloids; evoxine (10) and 7-(g,g-dimethylallyloxy)g-fagarine (11), among other compounds including the acridone alkaloids; tegerrardin A (12), tegerrardin B (13), arborinine (14), evoxanthine (15), 1,3-dimethoxy-N-methylacridone
(16) and tecleanone (17) from the stem bark of this plant and
This journal is © The Royal Society of Chemistry 2015
Measured
activity
Author, reference
Antibacterial
activity
Cheesman et al.24
Antimicrobial
activity
Pallant et al.32
Antimicrobial
activity
Juma et al.33
Antihypertensive Rafamantanana
activity
et al.40
Anti-malarial
activity
Antiplasmodial
activity
Cheplogoi et al.44
Waffo et al.46
tested their antiplasmodial activity against the CQS D10 strain
of P. falciparum.46 Compound 10 exhibited an IC50 of 24.5 mM,
while arborinine showed the best activitity (IC50 ¼ 12.3 mM).46
Sceletium tortuosum or Mesembryanthemum tortuosum
(Mesembryanthemaceae) is endemic to the Cape Region of
South Africa. This plant is one of South Africa's most popular
plants, mainly for its use of this plant as a mood-altering drug
RSC Adv., 2015, 5, 43242–43267 | 43245
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Review
Summary of the bioactivity of derived alkaloids (acridone, mesembrine and isoquinoline) versus ethnobotanical uses of plant species
derived from Southern Africa flora
Table 2
Compound
subclass
Isolated metabolites
Acridone
alkaloids
Tegerrardin A (12),
tegerrardin
B (13), arborinine (14),
evoxanthine (15), 1,3dimethoxy-Nmethylacridone (16) and
tecleanone (17)
Mesembrine Mesembrine (18),
mesembrenone (19),
mesembrenol (20) and
mesembranol (21)
Isoquinoline Norprotosinomenine
(22)
Plant
species
(country)
Teclea
gerrardii
(South
Africa)
Family
Ethnobotanical use
Measured
activity
Rutaceae
Bark decoctions are taken for
chest complaints45
Antiplasmodial Waffo
activity
et al.46
Sceletium Mesembryanthemaceae Used for centuries as a mood-altering drug,
used also in the management of psychiatric
tortuosum
and psychological conditions including
(South
depression, anxiety, drug dependence,
Africa)
bulimia and obsessive-compulsive
disorder47–49
Erythrina Leguminosae
The extracts from this plant have been used
lysistemon
in traditional medicine and have also
(Botswana)
shown antiviral, anticancer and cytotoxic
activities51,52
can be traced back probably to centuries.47 Due to the popularity
of this plant, whole plantations have been established and
diverse consumer products are commercially available from the
plant. The alkaloids of S. tortuosum (mainly mesembrine alkaloids) exhibit important pharmacological properties and are
used for the treatment of psychiatric and psychological conditions, including depression, anxiety, drug dependence, bulimia
and obsessive-compulsive disorder.47–49 Four alkaloids from this
sub-class; mesembrine (18), mesembrenone (19), mesembrenol
(20) and mesembranol (21) have been recognized for their
remarkable psychoactive properties.47,50 These compounds are
currently being used in pharmaceutical formulations for the
management of psychiatric and psychological conditions like
depression, anxiety, drug dependence, bulimia and obsessivecompulsive disorder.49 Moreover, mesembrine alkaloids have
a particular ability to treat conditions of the central nervous
system (CNS).50 This has been attributed to their capacity to act
as serotonin re-uptake inhibitors, thereby contributing to
regulating the balance of neurochemicals in the brain.51,52
Among the uses of Erythrina lysistemon (Leguminosae), the
extracts from this plant have been used in traditional medicine
and have shown antiviral, anticancer and cytotoxic activities.
The antimicrobial activity of the isoquinoline alkaloid precursor
norprotosinomenine (22), isolated from the plant harvested in
Botswana, partly justifying its use in ATM.33
3 Terpenoids from Southern African
flora
The summary of the most important ndings on the bioactive
terpenoids from Southern Africa ora have been given in Table
3–6 (according to their subclasses), while the chemical structures are shown in Fig. 2–8.
43246 | RSC Adv., 2015, 5, 43242–43267
3.1
Author,
reference
Psychoactive
activity
Shikanga
et al.50
Antimicrobial
activity
Juma
et al.33
Monoterpenoids and meroterpenoid
Mujovo et al. isolated the monoterpenes (E)-2(3)-tagetenone
epoxide (23), myrcenone (24) and piperitenone or 3-methyl-6-(1methylethylidene)-cyclohex-2-en-1-one (25) in addition to other
phytochemicals from Lippia javanica (Verbenaceae),53 an
aromatic herb that occurs all over Mozambique. Infusions of its
leaves is commonly used in Africa as a tea against various
ailments like inuenza, measles, rashes, malaria, stomach
problems, fever, colds, cough, headaches.54–57 In Botswana it is
used as a caffeine-free tea and in Zimbabwe and Malawi as a
nerve tonic.58 The compounds were tested against Mycobacterium tuberculosis and HIV reverse transcriptase. It was found
that (E)-2(3)-tagetenone epoxide (23) inhibited the HIV-1 reverse
transcriptase enzyme by 91% at 100 mg mL 1. Moreover, the
triterpene euscaphic acid, also isolated from this plant, was
found to exhibit a minimum inhibitory concentration of 50 mg
mL 1 against sensitive strain of M. tuberculosis, H37Rv, reference strain (27294). This rare monoterpene (compound 23) has
also been also identied in the Cameroonian Clausena anisata
(Rutaceae) essential oil.59 Compound 25 (3-methyl-6-(1methylethylidene)-cyclohex-2-en-1-one) was also noted to be
the major component of the essential oil from L. javanica harvested from South Africa.58 The oil was tested for antimicrobial
activity on cultures of Escherichia coli, Bacillus subtilis and
Staphylococcus aureus, and found to inhibit E. coli and S. aureus
at 1% dilution. The oil was also active against P. falciparum in
micromolar concentrations.58
Ptaeroxylon obliquum (Rutaceae), also known as sneezewood,
grows only in Southern Africa. This plant is traditionally used in
Southern Africa for the treatment of various ailments, including
headaches and tick control.60,61 Agostinho et al. isolated ptaerobliquol (26), a new monoterpene-chromone (or meroterpenoid) from the roots of this plant for the rst time.62 The
compound demonstrated a moderate activity when tested on
This journal is © The Royal Society of Chemistry 2015
Review
Fig. 1
Chemical structures of alkaloids from Southern African flora (1–22).
Toxoplasma gondii replication using CPRG-based colorimetric
assay,63 inhibiting parasite replication at 5 and 10 mM, with an
IC50 of 5.13 mM. Lower concentrations of the compound (0.1
and 1 mM) tested were totally inactive, while cellular toxicity
appears at concentration of 25 mM, giving ptaerobliquol a low
therapeutic index.
3.2
RSC Advances
Sesquiterpenes
Vernonia auriculifera (Asteraceae) is a small tree or woody herb
that grows between 1 and 7.5 m high and is easily recognizable
by its deep purple owers. This plant has a wide variety of uses
This journal is © The Royal Society of Chemistry 2015
in traditional medicine; a drop of the juice squeezed from the
crushed stem bark, inserted into the nostrils, is used to relieve
headache.64 The Kikuyu people of central Kenya use the leaves
of this plant as a wrap for pounded material used as a poultice,65
cold water infusion of the plant is administered orally in
Uganda and Kenya to treat fever associated with viral and
bacterial infections.66,67 In Ethiopia, the roots are used to treat
toothache68 and snake poison.69 Phytochemical investigation of
Vernonia auriculifera by Kiplimo et al. afforded farnesylamine
(27), a unique sesquiterpene amine not found previously in
plant species.70 The compound could not be screened for
RSC Adv., 2015, 5, 43242–43267 | 43247
Summary of the bioactivity of derived (monoterpenes, meroterpenoid and sesquiterpenes) versus ethnobotanical uses of plant species derived from Southern Africa flora
Compound
subclass
Monoterpenes
Meroterpenoid
Sesquiterpenes
Sesquiterpene
lactones
Author, reference
Its infusion is commonly used in Africa
as a tea against various ailments like
inuenza, measles, rashes, malaria,
stomach problems, fever, colds, cough,
headaches, in Botswana it is used as a
caffeine-free tea and in Zimbabwe and
Malawi as a nerve tonic54–57
Used in South Africa against various
chest ailments, inuenza, measles,
rashes, stomach problems and
headaches, depending on the traditional
healer, and is therefore known as fever
tea or musudzungwane in Tshivenda, its
essential oil has also been found to have
good insect repellent activity. In
Botswana it is used as a caffeine free tea.
In Zimbabwe and Malawi it is used
mainly as a nerve tonic54–57
Used in southern Africa for the treatment
of various diseases, from headaches to
tick control60,61
Antitubercular and
anti-HIV activity
Mujovo
et al.53
Antimicrobial
and antimalarial activity
Manenzhe
et al.58
Antiprotozoan activity
Agostinho
et al.62
Used as a poultice, to relieve headache, to
treat conjunctivitis, to treat fever
associated with viral and bacterial
infections, treat toothache and snake
poison65–68
Fruits were formerly used to poison
carcasses in order to destroy hyenas and
other vermin71
To treat a wide variety of kidney
infection, diarrhoea, cholera, coughs,
malaria, gynaecological disorders,
infertility, venereal diseases, cancer, and
insanity75,76
Antibacterial activity
Kiplimo
et al.70
Antibacterial activity,
cytotoxicity and
antioxidant activity
Antimicrobial activity
Momtaz
et al.71
Treatment of coughs
and colds, fevers, ulcers, dermatosis,
venereal diseases, labour pains,
dysentery, intestinal parasites, stomach
pains, toothache and internal worms82
Antimalarial
activity
Plant species (country)
Family
Ethnobotanical use
(E)-2(3)-Tagetenone epoxide (23),
myrcenone (24), piperitenone or
3-methyl-6-(1-methylethylidene)cyclohex-2-en-1-one (25)
Lippia javanica
(Mozambique)
Verbenaceae
Piperitenone or 3-methyl-6-(1methylethylidene)-cyclohex-2-en-1-one
(25), major component
of the essential oil
Lippia javanica
(South Africa)
7a,8,9,9a,9b,10b-Heptahydro-4H-10,10dimethyl-1,7-dioxa-5-hydroxy-2hydroxymethylcyclobutyl[1,2,3:3,3a,4]
indeno[5,6-a]naphtalen-4-one or
ptaerobliquol (26)
Farnesylamine (27)
Ptaeroxylon obliquum
(Mozambique)
Rutaceae
Vernonia auriculifera
(South Africa)
Asteraceae
Tutin (28) and hyenanchin (29)
Hyaenanche globosa
(South Africa)
Euphorbiaceae
1b-Furanoyloxy-9a-benzoyloxy-dihydro-bagarofuran (30), 1a-furanoyloxy-9bbenzoyloxy-2-oxo-dihydro-b-agarofuran
(31), 1b,9a-difuranoyloxy-8b-acetoxy-2oxo-3-ene-dihydro-b-agarofuran (32), 1bfuranoyloxy-9a-benzoyloxy-8b-acetoxy-2oxo-3-ene-dihydro-b-agarofuran (33) and
1b,9a-difuranoyloxy-2,8-dioxo-3-enedihydro-b-agarofuran (34)
3-Oxoeudesma-1,4(15),11(13)-triene12,6a-lide (35)
Osyris lanceolata
(Botswana)
Santalaceae
Dicoma anomala
(South Africa)
Asteraceae
Yeboah
et al.77
Becker
et al.87
Review
This journal is © The Royal Society of Chemistry 2015
Dihydro-bagarofuran
sesquiterpene
polyesters
Measured
activity
Isolated metabolites
RSC Advances
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Table 3
Review
This journal is © The Royal Society of Chemistry 2015
Table 4 Summary of the bioactivity of derived (abietane diterpenes, labdane-type diterpenes, limnoid diterpenes and kaurene diterpenes) versus ethnobotanical uses of plant species derived
from Southern Africa flora
Compound
subclass
Isolated
metabolites
Plant species
(country)
Abietane
diterpenes
Parviorone D (36)
and parviorone F (37)
11-Hydroxy-19-(methyl-buten-2-oyloxy)abieta-5,7,9
(11),13-tetraene-12-one (38)
11-Hydroxy-19-(4-hydroxy-benzoyloxy)abieta-5,7,9(11),13-tetraene-12-one (39)
and 11-hydroxy-19-(3,4-dihydroxybenzoyloxy)-abieta-5,7,9(11),13-tetraene12-one (40)
9,13-Epoxy-6-hydroxy-16,15-labdanolide
(41) and 9,13:15,16-diepoxy-6,16labdanediol (42)
Plectranthus ecklonii
(South Africa)
Plectranthus lucidus
(South Africa)
Labdane-type
diterpenes
ent-14S*-Hydroxykaur-16-en-19-oic (50),
ent-14S*,17-dihydroxykaur-15-en-19-oic
(51), ent-kaur-16-en-19-oic acid (52), entkaur-16-en-19-al (53), ent-12bhydroxykaur-16-en-19-oic acid (54), ent12b-acetoxykaur-16-en-19-oic acid (55)
Lamiaceae
Ethnobotanical
use
Measured
activity
Author,
reference
For treatment of gastro-intestinal
disorders, as anti-microbial agents for
the treatment of wounds, the
alleviation of respiratory
conditions and for malaria90–97
Antiplasmodial activity
van Zyl et al.98,99
Treating colds, bronchitis,
tuberculosis, coughs, asthma,
feverish headaches, dysentery
and chest infections101–104
Used in folk medicine as a
poison against snakes107,108
Antimycobacterial activity
Naidoo et al.106
Mutagenic activity,
cytotoxic activity and
genotoxicity
Sebastião et al.109
Plectranthus tongaensis
(South Africa)
Leonotis leonurus
(South Africa)
Eragrostis viscose
(Angola)
Poaceae
Vepris uguenensis
(Kenya)
Croton pseudopulchellus
(South Africa)
Rutaceae
Treatment of malaria118
Antimalarial activity
Cheplogoi et al.119
Euphorbiaceae
A decoction from the roots is
used to treat asthma, the
powdered root
taken as a snuff for headaches and
leaves are applied by
Tanzanians to their chest for chest
ailments57,120–124
Antiviral, cytotoxicity and
antiplasmodial activity
Langat et al.125
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Limonoid
diterpenoid
Kaurene
diterpene
Methyl-8a,15-epoxylabdan-16b-oate (43),
8a,15-epoxylabdan-16b-ol (44), 8a,15epoxy-16-norlabdan-13b-ol (45), 8a,15epoxy-16-norlabdan-13-one (46), 8a,15epoxylabdan-16b-oic acid (47) and 16acetoxy-8a,15-epoxylabdane (48)
Methyl uguenesonate (49)
Family
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43250 | RSC Adv., 2015, 5, 43242–43267
Table 5
Summary of the bioactivity of derived pentacyclic triterpenoids versus ethnobotanical uses of plant species derived from Southern Africa flora
Compound
subclass
Isolated
metabolites
Plant species
(country)
Pentacyclic
triterpenoids
Lupenyl acetate (56), oleanolic acid (57),
b-amyrin acetate (58), a-amyrin (59) and
b-amyrin (60), friedelanone (61) and
friedelin acetate (62).
Vernonia auriculifera
(Kenya)
a-Myrin (59) and betulinic acid (63)
Artemisia afra
(South Africa)
Lup-20(30)-ene-3a,29-diol (64), lup20(29)-ene-30-hydroxy-3-one (65) and Jtaraxastanonol (66)
Elaeodendron
transvaalense
(South Africa)
Celastraceae
1a,23b-Dihydroxy-12-oleanen-29-oicacid-23b-O-a-4-acetylrhamnopyranoside
(67) and 1,22-dihydroxy-12-oleanen-30oic acid (68)
67 and 68
Combretum padoides
(South Africa)
Combretaceae
Lupeol (69)
Asteraceae
Ethnobotanical
use
Measured
activity
Author,
reference
Used as a poultice, to relieve headache, to
treat conjunctivitis, to treat fever
associated with viral and bacterial
infections, treat toothache and snake
poison64–69
To treat coughs, colds, diabetes, malaria,
sore throat, asthma, headache, dental
care, gout and intestinal worms131–133
To treat coughs, diarrhoea, stomach
ailments, herpes and sexually associated
diseases, treatment of arthritis, cancer
and precbribed presently for HIV/AIDS139
Use in traditional medicine for relieving
symptoms that appear to be caused by
infective agents e.g. bloody diarrhoea,
wounds and conjunctivitis142
Antibacterial activity
Kiplimo et al.70
Antimicrobial activity
More et al.137
Cytotoxicity activity
Tshikalange et al.138
Antibacterial activity
Angeh et al.144
Eloff et al.145
Use traditional in South Africa to treat
diabetic146
Treating abdominal disorders, backache,
bacterial infections etc.147
Antidiabetic activity
Nkobole et al.146
Antimicrobial activity
Eloff et al.145
Review
This journal is © The Royal Society of Chemistry 2015
1,3-Dihydroxy-12-oleanen-29-oic (70), 1hydroxy-12-olean-30-oic acid (71), 3,30dihydroxyl-12-oleanen-22-one (72),
1,3,24-trihydroxyl-12-olean-29-oic acid
(73) and 1,23-dihydroxy-12-oleanen-29oicacid-3-O-2,4-di-acetyl-1rhamnopyranoside (74)
Combretum padoides
(South Africa)
Terminalia sericea
(South Africa)
Combretum imberbe
(Zimbabwe)
Family
Summary of the bioactivity of derived pentacyclic triterpenoids versus ethnobotanical uses of plant species derived from Southern Africa flora
Compound
subclass
Isolated
metabolites
1a,3,b-Hydroxyimberbic acid-23-O-a-L-4Pentacyclic
triterpenoids acetylrhamnopyranoside (75),
1a,3,b-hydroximberbic acid-23-O-a-L3,4-diacetylrhamnopyranoside (76),
1a,3,b-hydroxyimberbic acid-23a-[L-3,4-diacetyl-rhamnopyranosyl]-29-Oa-rhamnopyranoside (77), and 1,3,hydroxyimberbic acid (78)
75 and 1a,3,b-hydroxyimberbic acid-23O-a-[L-4-acetyl-rhamnopyranosyl]-29-O-arhamnopyranoside (79)
Terminaliaside A (80), arjunglucoside I
(81) and sericoside (82)
3b-(5-Hydroxyferuloyl)-Lup-20(30)-ene
(83), lupene (84), 69 and betulin (86)
Plant species
(country)
Combretum imberbe
(Zimbabwe)
Combretaceae
Terminalia stuhlmannii
(Zimbabwe)
Terminalia tropophylla
(Madagascar)
Euclea divinorum
(Zimbabwe)
69, 86 and a-amyrin-3-O-b-(5-hydroxy)
ferulic acid (87)
3b-(300 ,400 -Dihydroxy)-(E)cinnamoyloxylup-20(29)-ene (88)
Euclea undulate
(South Africa)
Eragrostis viscose
(Angola)
1b,3b,11a,26-Tetrahydroxy-7,24Eeuphadiene (89), 3b,26-dihydroxy-8,24Eeuphadien-11-one (90) and (24S)1b,3b,24,25-tetrahydroxy-7,9(11)euphadiene (91)
Friedelin (92)
Cassipourea lanceolata
(Madagascar)
Ebenaceae
Poaceae
Ethnobotanical
use
Measured
activity
Author,
reference
Used in African traditional medicine
for diverse uses23,27,148–150
Antimicrobial activity
Katererea et al.151
Used in African
traditional medicine
for diverse uses154–158
Used in African traditional
medicine for diverse uses154–158
Bark of the roots is used in
the treatment of diarrhoea,
convulsions, cancer, skin
diseases and gonorrhoea.26,85
Treatment of diabetes165,166
Antimicrobial activity
Katererea et al.151
Used in folk medicine as a poison
against snakes107,108
Mutagenic activity,
Sebastião et al.109
cytotoxic activity,
genotoxicity activity
Antiproliferative activity Hou et al.169
Rhizophoraceae Not specied
Clusiaceae
Garcinia goudotiana
(Madagascar)
Pittosporum verticillatum Pittosporaceae
(Madagascar)
Used for antiparasitic, antitussive
and antimicrobial properties171
Some species are used in traditional
medicine as anti-inammatory,
antimicrobial and antispasmodic
agents173
Antiproliferative activity Cao et al.153
Cytotoxicity
Mebe et al.163
Hypoglycaemic activity
Deutschländer et al.167
Antimicrobial and
cytotoxic activity
Cytotoxicity
Sania et al.171
Mahenina et al.175
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3-O-[b-D-Glucopyranosyl-(1/2)]-[a-Larabinopyranosyl-(1/3)]-[a-Larabinofuranosyl-(1/4)]-b-Dglucuronopyra-nosyl-21-O-(2-acetoxy-2methylbutanoyl)-R1-barrigenol (93), 3-O[b-D-glucopyranosyl-(1/2)]-[a-Larabinopyranosyl-(1/3)]-[a-Larabinofuranosyl-(1/4)]-b-Dglucuronopyranosyl-21-O-(2-acetoxy-2methylbutanoyl)-28-O-acetyl-R1barrigenol (94), 3-O-[b-D-glucopyranosyl(1/2)]-[a-L-arabinopyranosyl-(1/3)][a-L-arabinofuranosyl-(1/4)]-b-Dglucuronopyra-nosyl-21-O-b,bdimethylacryloyl-22-O-angeloyl-R1barrigenol (95) and senaciapittoside B
(96)
Family
Review
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Table 6
RSC Advances
antibacterial activity (with the goal of validating its ethnobotanical use) due to sample decomposition. However, in addition
to the triterpenoids (lupenyl acetate, oleanolic acid, b-amyrin
acetate, b-amyrin, friedelanone, friedelin acetate, a-amyrin and
b-sitosterol) present in the plant material, there is potential for
synergistic coupling with antimicrobial agents to improve
therapeutic efficiency.70
Two sesquiterpenes (28 and 29) have also been isolated from
Hyaenanche globosa (Euphorbeaceae), a narrow endemic
poisonous plant restricted to a single at-topped mountain near
Van Rhynsdrop in southern Namaqualand. In vitro studies of
the ethanolic extract of the fruits of the plant displayed a
signicant anti-tyrosinase, antibacterial, and cytotoxic effects.
Momtaz et al. isolated the tutin (28) and hyenanchin or mellitoxin (29) from the ethanolic extract of the fruits of the plant
which did not exhibit any signicant cytotoxic effects on the on
‘Hela cells’.71 This could be explained by the fact that the
Fig. 2
Review
compounds responsible for the activity were not isolated and
that activity in the crude extract is due to synergy. It has been
reported by several studies that compound 28 is the major
neurotoxin in the New Zealand shrubs of the genus Coriaria and
compound 29 is a major active component in toxic honey.72–74
The shrub Osyris lanceolata (Santalaceae), also called ‘African
sandalwood’, is used in traditional medicine in Botswana,
South Africa, East Africa, Ethiopia and parts of Asia to treat a
wide variety of diseases including; kidney infection, diarrhoea,
cholera, coughs, malaria, gynaecological disorders, infertility,
venereal diseases, cancer, and insanity. The ethnomedicinal
applications of Osyris species in traditional medicine
has been published in different parts of the world, including
the NAPRALERT database75 and the Prelude Medicinal
Plants Database.76 Yeboah et al. isolated ve new dihydro-bagarofuran polyesters from the root bark and stem bark of the
plant, harvested in Botswana.77 The compounds include 1b-
Chemical structures of monoterpenes, meroterpenoid and sesquiterpenes from Southern African flora (23–35 and 102–104).
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Review
furanoyloxy-9a-benzoyloxy-dihydro-b-agarofuran (30), 1a-furanoyloxy-9b-benzoyloxy-2-oxo-dihydro-b-agarofuran (31), 1b,9adifuranoyloxy-8b-acetoxy-2-oxo-3-ene-dihydro-b-agarofuran (32),
1b-furanoyloxy-9a-benzoyloxy-8b-acetoxy-2-oxo-3-ene-dihydro-bagarofuran (33) and 1b,9a-difuranoyloxy-2,8-dioxo-3-ene-dihydro-b-agarofuran (34). The compounds have received considerable attention recently and they are considered as ‘privileged
structures’ because they typically display multiple pharmacological activities due to their unique framework that can provide
ligands to interact with multiple receptors. They have been
reported to have insecticidal, anti-HIV, anti-cancer, multidrug
resistance (MDR) reversal and acetylcholinesterase (AChE)
inhibition activities in literature.78–81
3.3
Sesquiterpene lactones
Dicoma anomala (Asteraceae) is a grassland species widely
distributed in sub-Saharan Africa. This plant was selected by
the national consortium initiative to discover novel antiplasmodial agents from South African plants based on its
ethnomedicinal prole.82 The EtOAc extract of the plant
exhibited an IC50 of 1.4 mg mL 1 on the chloroquine-sensitive
D10 strain on P. falciparum using the pLDH assay.83 The plant
also has a wide range of ethnomedicinal applications,
including the treatment of coughs and colds, fevers, ulcers,
dermatosis, venereal diseases, labour pains, dysentery, intestinal parasites, stomach pains, toothache and internal worms.
D. anomala can also be linked to several pharmacological
properties: anti-bacterial, anti-helmintic, anti-viral, anti-
RSC Advances
plasmodial, anti-spasmodic, wound healing, analgesic and
anti-inammatory.83–86 Becker et al. isolated a eudesmanolidetype sesquiterpene lactone, 3-oxoeudesma-1,4(15),11(13)triene-12,6a-lide (35), commonly named dehydrobrachylaenolide, as the main active constituent of the extract.87 The
identied compound was previously isolated from the roots of
Brachylaena transvaalensis. The compound showed an in vitro
IC50 of 1.865 mM against a chloroquine-sensitive strain (D10) of
P. falciparum. The activity of the compound against the
chloroquine-sensitive strain (IC50 ¼ 1865 nM) is within an
order of magnitude of that of quinine (IC50 ¼ 194 nM).88 In
addition, the compound had a therapeutic index of 9.2 against
the chloroquine-sensitive strain, which is close to the acceptable value of 10 for potential development.89 Thus the
compound can be considered as a hit, because it complies with
the basic criteria for anti-parasitic drug discovery89 with an in
vitro IC50 against whole protozoa of #1 mg mL 1 and a selectivity of close to ten-fold more against the chloroquinesensitive parasites than against the Chinese hamster ovary
(CHO) cells.
3.4
Abietane diterpenes
Plectranthus species have found wide applications in African
traditional medicine (ATM), for example, in the treatment of
gastro-intestinal disorders,90 as anti-microbial agents,91
for the treatment of wounds,92 the alleviation of respiratory
conditions93 and for malaria treatment.92,94–97 Zyla et al.
isolated the abietane diterpenes; 11-hydroxy-2a-(4-hydroxy-
Chemical structures of abietane diterpenes, labdane-type diterpenes, limnoid diterpenes and kaurene diterpenes from Southern African
flora (36–48).
Fig. 3
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benzoyloxy)-abieta-5,7,9(11),13-tetraene-12-one or parviorone
D (36) and 11-hydroxy-2a-(3,4-dihydroxybenzoyloxy)-abieta5,7,9(11),13-tetraene-12-one or parviorone F (37) from the
leaves Plectranthus ecklonii (Lamiaceae).98 The compounds were
tested for their antiplasmodial activity against a chloroquineresistant strain of P. falciparum and for their ability to inhibit
b-haematin formation. The compounds were less active relative
to chloroquine and quinine, but showed signicant activity in
the inhibition of b-haematin formation. The tritiated hypoxanthine incorporation assay99 was used to determined antimalarial activity of the isolated compounds, with sodium
stibogluconate (IC50: 10.6 nM) as the control drug. When
compared to the isolated abietane diterpenes, there was a 15fold decrease in activity. Compound 37 (IC50 ¼ 3.11 mM) had the
lowest IC50 values and was more effective than quinine, with
compound 36 being 62% as active as chloroquine, with
(IC50 ¼ 5.3 mM).98 Zyla et al. also isolated the
known compounds 11-hydroxy-19-(methyl-buten-2-oyloxy)abieta-5,7,9(11),13-tetraene-12-one (38) and compound 36
from the Plectranthus species; Plectranthus tongaensis (Lamiaceae)98 cultivated in many household gardens in South Africa.
The anti-plasmodial activities were evaluated, compounds 36
and 38 having IC50 values of 5.3 mM and 6.0 mM respectively.
Another set of abietane diterpenes isolated by Zyla et al. from
Plectranthus tongaensis (Lamiaceae) and tested similarly
as above include 11-hydroxy-19-(4-hydroxy-benzoyloxy)-abieta5,7,9(11),13-tetraene-12-one (39) and 11-hydroxy-19-(3,4-dihydroxy-
Fig. 5 Chemical structures of triterpenoids from Southern African
flora (56–66).
Fig. 4 Chemical structures of abietane diterpenes, labdane-type
diterpenes, limnoid diterpenes and kaurene diterpenes from Southern
African flora (49–55).
43254 | RSC Adv., 2015, 5, 43242–43267
benzoyloxy)-abieta-5,7,9(11),13-tetraene-12-one (40).98 Compound
40 was more active than quinine with an IC50 value of 4.7 mM
compared to compound 39 with an IC50 value of 14.7 mM when
screened against chloroquine-resistant strain of Plasmodium
falciparum. These results justify the use of Plectranthus sp. in the
treatment of malaria among other uses.
This journal is © The Royal Society of Chemistry 2015
Review
3.5
Labdane-type diterpenes
Leonotis leonurus (Lamiaceae) commonly known as Wild dagga
or Lion's ear, is a robust perennial shrub which grows usually to
2 m tall and widely distributed in eastern South Africa, growing
amongst rocks in grassland.100 This plant has a wide variety of
medicinal uses, for example the treatment of cold,101 bronchitis,
tuberculosis,57 coughs, asthma,102 feverish headaches,103
dysentery and chest infections.104 Based on its ethnomedicinal
prole as a respiratory ailments, and it's in vitro antibacterial
activity,105 the plant has been identied as a potential source of
novel anti-tuberculosis compounds. Naidoo et al. isolated the
two new labdane-type diterpenoids; 9,13-epoxy-6-hydroxy-16,15labdanolide (41) and 9,13:15,16-diepoxy-6,16-labdanediol (42)
from the leaves of this plant.106 The compounds have relevance
as chemotaxonomic markers even though they showed no
activity against M. tuberculosis.106
The nutritive value of Eragrostis species (Poaceae) has been
reported in literature.107,108 Eragrostis viscosa (Poaceae) is used in
folk medicine as a poison against snakes in Angola but the plant
is not eaten by cattle. Phytochemical investigation of the
toluene and dichloromethane extracts of the aerial parts of this
plant by Sebastião et al. afforded three new 8a,15-epoxylabdanes namely; methyl 8a,15-epoxylabdan-16b-oate (43),
8a,15-epoxylabdan-16b-ol
(44),
8a,15-epoxy-16-norlabdan13b-ol (45) together with other known compounds.109 Some of
the known compounds in this class include 8a,15-epoxy-16norlabdan-13-one (46), 8a,15-epoxylabdan-16b-oic acid (47)
and 16-acetoxy-8a,15-epoxylabdane (48). The genotoxicity of the
compounds isolated from this plant was studied using a
cytokinesis-block micronucleus assay and the Ames test was
Fig. 6
RSC Advances
also used to assess mutagenicity. Compounds 44, 46 and 48
gave negative results on both assays and compound 44 was the
most cytotoxic of the tested compounds using MTT assay.
3.6
Limonoid diterpenoids
Among medicinal plants growing in Africa, limonoids, having
anti-malarial properties, are common a number of plant genera,
including Vepris (Rutaceae), Khaya (Meliaceae) and Entandrophragma (Meliaceae).20 Vepris species are used in ethnomedicine for the treatment of a diverse range of ailments,
including pneumonia, lung diseases and kidney disorders,110
eye troubles, cardiac pains, coughs, colds and inuenza,111,112
headache,113 menorrhegia and infertility,114 and as an aphrodisiac,115 diuretic and antipyretic,116 astringent and fortier,117
tonic for angina and rheumatism,112 and both orally and
externally as a treatment for malaria.118 Vepris uguenensis
(Rutaceae), also known as “chemchir” by the Pokot tribe of
Kenya, use this plant to treat malaria. Cheplogoi et al. isolated a
novel limonoid, methyl uguenesonate (49) together with other
compounds from the dichloromethane extract of the roots of
this plant.119 The compound displayed mild activity, with IC50
values of 10.4 and 13.8 mg mL 1, against the CQS and CQR
strains of P. falciparum, respectively, thus partly justifying its
use in malaria treatment locally.
3.7
Kaurene diterpenes
Croton pseudopulchellus (Euphorbiaceae), commonly known as
the Small Lavender Croton, is a shrub that grows to about 4 m
tall and it is widely distributed in drier woodlands of the warmer
Chemical structures of triterpenoids from Southern African flora (67–73).
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Review
Fig. 7 Chemical structures of triterpenoids from Southern African flora (74–84 and 86).
regions of East, South-central and parts of West Africa.120,121
This plant is used in the coastal area of Kenya as a spice when
material is burnt and the smoke used to avour fresh milk.122
Species of this plant are durable and are used for hut building
in Tanzania.123 A decoction from the roots of this plant is used
to treat asthma57,124 and the powdered root taken as a snuff for
headaches.120 Leaves are applied by Tanzanians to their chest
for chest ailments.120 Langat et al. isolated two new ent-kauren19-oic acid derivatives; ent-14S*-hydroxykaur-16-en-19-oic (50),
ent-14S*,17-dihydroxykaur-15-en-19-oic (51) together with some
of the known compounds; ent-kaur-16-en-19-oic acid (52), ent-
43256 | RSC Adv., 2015, 5, 43242–43267
kaur-16-en-19-al (53) ent-12b-hydroxykaur-16-en-19-oic acid (54)
and ent-12b-acetoxykaur-16-en-19-oic acid (55) from the hexane
and methylene chloride extracts of the stem bark of this
plant.125 Quantitative assessment of anti-plasmodial activity in
vitro was determined via the parasite lactate dehydrogenase
assay using a modied method described by Makler et al.126
Compound 54, the major constituent was tested in duplicate
against the chloroquine sensitive (CQS) strain of P. falciparum
(D10) and showed weak activity against the P. falciparum (CQS)
D10 strain. Compounds 50, 52, 54, and 55 were found to be
inactive when tested for their effects on Semliki Forest virus
This journal is © The Royal Society of Chemistry 2015
Review
Fig. 8 Chemical structure of methyljuglone.
replication and for cytotoxicity against human liver tumour cells
(Huh-7 strain).
3.8
Pentacyclic triterpenoids
Vernonia species are known to be rich in terpenoids, particularly
triterpenes and sesquiterpenes.20 Vernonia auriculifera (Asteraceae) is a small tree or woody herb that has wide variety of uses
in traditional medicine.64–69 Vernonia species extracts have been
cited as antimicrobials in traditional medicine.127 Sequential
extraction of the leaves, stem bark and root bark of this plant
using organic solvents; hexane, dichloromethane, ethyl acetate
and methanol by by Kiplimo et al. afforded the triterpenoids
lupenyl acetate (56), oleanolic acid (57), b-amyrin acetate (58),
a-amyrin (59) and b-amyrin (60) friedelanone (61) and friedelin
acetate (62) together with some other compounds.70 The antibacterial activities of the isolated compounds were determined
using the broth microdilution method as described by
Andrews.128 Four strains of Gram-negative and ve Grampositive bacteria strains were used to determined the antimicrobial activity. The compounds demonstrated moderate antibacterial activity; compounds 59 and 60 had minimum
inhibitory concentration (MIC) of 0.25 mg mL 1 against
Staphylococcus aureus, Bacillus subtilis, Enterococcus faecium and
Staphylococcus saprophyticus while compounds 56 and 57
exhibited MIC of 0.25 mg mL 1 against Stenotrophomonas
maltophilia. The oleanane triterpernoids 57, 58 and 60 displayed better antibacterial activity than the friedelane triterpenoids 61–62. It is reported that the 28-COOH and ester
functionality at C-3 contributes to pharmacological activities of
pentacyclic triterpenes129 like lupenyl which has greater antimutagenic activity than compound 56.130 These effects are
observed for 61 and 62 where the ketone has higher activity
against B. subtilis than the ester.
Other triterpenes correlating biological activity and ethnobotanical uses of species from the Artemisia genus. As a typical
example, the ethnobotanical uses of A. afra (Asteraceae) have
been investigated by van Wyk et al.131–133 The African wormwood,
A. afra, is a common species in South Africa with a wide
distribution from the Cederberg Mountains in the Cape,
northwards to tropical East Africa and stretching as far north as
Ethiopia.131,132 In southern Africa, this plant is used to treat
coughs, colds, diabetes, malaria, sore throat, asthma, headache, dental care, gout and intestinal worms.133 In vitro studies
of this plant have revealed that the plant is a potential antidepressant, cardiovascular, spasmolytic effects, antioxidant, and
antimycobacteria.134–136 The crude ethanolic extract of this plant
This journal is © The Royal Society of Chemistry 2015
RSC Advances
exhibited strong antimicrobial activity by inhibiting the growth
of all tested microbial species at concentration range of 1.6 mg
mL 1 to 25 mg mL 1 thus prompted the further investigation.
More et al. isolated compound 59 and betulinic acid (63) from
this plant and other known compounds.137 The compounds
were evaluated for antimicrobial activity against Gram positive
(Actinomyces naeslundii, Actinomyces israelii, and Streptococcus
mutans), Gram negative bacteria (Prevotella intermedia, Porphyromonas
gingivalis
and
Aggregatibacter
actinomycetemcomitans
previously
known
as
Actinobacillus
actinomycetemcomitans), and Candida albicans. The isolated
compounds showed activity range at 1.0 mg mL 1 to 0.25 mg
mL 1. Compound 63 was one of the best compounds that
showed good antimicrobial activity and the antioxidant activity
was done on the compound using the DPPH scavenging
method. The result revealed that compound 63 exhibited a
decreased scavenging activity with an IC50 of 2.42 mg mL 1.
Compound 63 showed a smooth trend of non-toxic effects with
IC50 value 30.96 of mg mL 1. Thus the results obtained in this
study conrm the use of this plant in the treatment of microbial
infections.
Tshikalange et al. isolated the three known triterpenoids lup20(30)-ene-3a,29-diol (64), lup-20(29)-ene-30-hydroxy-3-one (65)
and J–taraxastanonol (66) together with other known
compounds from stem bark of Elaeodendron transvaalense
(Celastraceae), collected from Venda (Northern Limpopo),
South Africa.138 Extracts from this plant have been used in
traditional medicine by the Vhavenda people of South Africa
(Limpopo province) to treat coughs, diarrhoea, stomach
ailments, herpes and sexually associated diseases. The stem
bark is mostly used to prepare infusions and decoctions.139 This
plant is also used in the treatment of arthritis, cancer, coughs,
diarrhoea and stomach ailaments and is being prescribed
presently to people who are suffering from HIV/AIDS by traditional healers.140 The cytotoxicity of the isolated compounds was
determined using XTT colorimetric assay against Vero and
MCF-7 breast cancer cell lines.141 Compounds 64 and 66 showed
weaker activities with the IC50 ranging from 66.6 to over 100.00
mg mL 1 in both cell lines, while compound 65 exhibited a good
cytotoxicity activity IC50 value of 25.1 mg mL 1 for Vero cells and
19.4 mg mL 1 for breast cancer cell line. The cytotoxicities of the
isolated compounds (64–66) may partly justify the use of E.
transvaalense in the treatment of several ailments in ATM,
including cancer related problems.139
Some Combretum species have been used in traditional
medicine for relieving symptoms that appear to be caused by
infective agents like bloody diarrhoea, wounds and conjunctivitis.142 This conrms the preliminary data gathered by Eloff,143
which demonstrated that crude extracts of Combretum padoides
(Combretaceae) were active against the four most important
nosocomial bacterial pathogens. Angeh et al. isolated a
new oleanene-type triterpenoid glycoside known as 1a,23b-dihydroxy-12-oleanen-29-oic-acid-23b-O-a-4-acetylrhamnopyranoside (67), 1,22-dihydroxy-12-oleanen-30-oic acid (68) and a
known steroids from the dichloromethane extract of this plant
using antibacterial activity guided fractionation against
Staphylococcus aureus.144 Compounds 67 and 68 exhibited a
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reasonable antibacterial activity with MIC of 0.031 and 0.063 mg
mL 1 against S. aureus and Escherichia coli. This result conrms
the antibacterial activity of this plant that the isolated triterpenes are non-cytotoxic.144 Eloff et al. also isolated
compounds 67 and 68 from this same plant using bioassayguided fractionation.145 The compounds demonstrated a
reasonable antibacterial activity as described Angeh et al.,144
which could partly justify its use in the treatment of wounds and
other infectious diseases.
Terminalia sericea (Combretaceae) stem bark extract showed
the best results against a-glucosidase and a-amylase enzymes in
an in vitro screening exercise of a number of South African
medicinal plants, in an attempt to discover new antidiabetic
agents. A bioassay-guided fractionation of an acetone extract of
the stem bark of this plant by Nkobole et al. led to the isolation
of lupeol (69) and other known compounds.146 The result
demonstrated that compound 69 was one of the secondary
metabolite that showed the best inhibitory activity on a-glucosidase with an IC50 value of 66.48 mM. Additionally, bioevaluation of compound 69 inhibitory activity on a-amylase
demonstrated that the compound had an IC50 value of 140.72
mM against the enzyme, thus validating the use of the plant in
traditional medicine to treat diabetic in South Africa.
Combretaceae species are widely traded in the traditional
medicine market in Southern Africa and are used medicinally in
several continents in the world.147 Traditional healers in Eastern
and Southern Africa have used Combretum species, for many
applications including treating abdominal disorders, backache,
bacterial infections, bilharzia, cancer, chest coughs, cleansing
the urinary system, colds, conjunctivitis, constipation, diarrhoea, dysentery, dysmenorrhoea, earache, fever, gastric ulcers,
general weakness, gonorrhoea, headaches, heart diseases,
hookworm, hypertension, jaundice, leprosy, nosebleeds,
oedema, pneumonia, skin diseases, sore throats, stomach and
gastric problems, swelling caused by mumps, syphilis, toothache, venereal diseases.23,27,148–150 Extract from Combretum
imberbe (Combretaceae) leaves, obtained using intermediate
polarity extractants, had reasonable to very good activity with
MICs as low as 40 mg mL 1, thus validating the traditional use of
the plant in the treatment of infectious diseases. Five antibacterial triterpenoids; 1,3-dihydroxy-12-oleanen-29-oic (70), 1hydroxy-12-olean-30-oic acid (71), 3,30-dihydroxyl-12-oleanen22-one (72), 1,3,24-trihydroxyl-12-olean-29-oic acid (73) and
1,23-dihydroxy-12-oleanen-29-oicacid-3-O-2,4-di-acetyl-1-rhamnopyranoside (74) were isolated from the leaves of this plant. The
compounds had levels of antibacterial activity MIC values
against S. aureus and E. coli ranging from 16 to 62 mg mL 1.
ref. 145 and 147 The antibacterial activity of the isolated
compounds was much lower than expected from the activity of
the crude extracts this can be due to synergy. Katererea et al.
also isolated the two novel derivatives of 1a,3b,23trihydroxyolean-12-en-29-oic acid; 1a,3,b-hydroxyimberbic acid23-O-a-L-4-acetylrhamnopyranoside (75), 1a,3,b-hydroximberbic
acid-23-O-a-L-3,4-diacetylrhamnopyranoside (76) and the
known compounds 1a,3,b-hydroxyimberbic acid-23-a-[L-3,4diacetyl-rhamnopyranosyl]-29-O-a-rhamnopyranoside (77), and
1,3-hydroxyimberbic acid (78) form the leaves of the this
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plant.151 The antimicrobial activity of the isolated compounds
was done using a microtitre dilution assay (MDA),152 showing.
Compound 77 to have inhibitory activity against P. vulgaris (12.5
mg mL 1) and S. aureus (6.25 mg mL 1). Compound 75 inhibited
S. aureus at 12.5 mg mL 1, while compound 76 inhibited S.
aureus at 6.25 mg mL 1 and M. fortuitum at 12.5 mg mL 1.
Compound 78, the free aglycone, showed activity against
Mycobacterium fortuitum at a concentration of 1.56 mg mL 1 and
S. aureus at 3.13 mg mL 1, which was a surprising case because
the Mycobacterium was generally resistant to the other test
samples. The activity of these compounds validates the use of
this plank in folk medicine. Escherichia coli was resistant to
these compounds, thus the constituents of these species of
Combretaceae may not be active against Gram negative
bacteria.
Katererea et al. isolated compound 75 and 1a,3,b-hydroxyimberbic acid-23-O-a-[L-4-acetyl-rhamnopyranosyl]-29-O-a-rhamnopyranoside (79) from the stem bark of this plant.151 Thus, this
study established that there is a chemotaxonomic link between
the genus Combretum and Terminalia due to the occurrence of
the trihydroxy-olean-12-en-29-oate aglycone; compound 75 and
79 in the species which had not been previously reported. The
isolated compounds were screened using a microtitre dilution
assay (MDA).152 Compound 79 was active against Candida albicans (12.5 mg mL 1) and S. aureus to a lesser extent (25 mg mL 1).
In the search for bioactive compounds from the Madagascar
forests as part of an International Cooperative Biodiversity
Group (ICBG) program, extracts of the roots of Terminalia tropophylla (Combretaceae) were screened and exhibited an
activity against the A2780 ovarian cancer cell line, with an IC50
value of 11 mg mL 1.153 Some metabolites isolated from Terminalia species have shown a wide range of biological activities,
including antimalarial,154 antifungal,154–156 antibacterial,155–157
and cytotoxic activities.156,158 Cao et al. isolated the new
oleanane-type triterpenoid saponin terminaliaside A (80), the
known triterpenoids saponins; arjunglucoside I (81), sericoside
(82) and a lignan derivative form the roots of this plant.153 The
compounds were tested in the A2780 assay. Compound 80 was
the most active with an IC50 value of 1.2 mM, while compound 81
was weakly active with an IC50 value of 16.5 mM and compounds
82 inactive with IC50 values >30 mM. The antiproliferative
activity of compound 80 is enhanced by substituents at the 3-,
16-, 21-, and 28-positions.159 The activity of the isolated
compounds provides the importance of oleanane-type saponins
as potential anticancer agents for further investigation.
Euclea divinorum (Ebenaceae) root bark is used in traditional
medicine for the treatment of diarrhoea, convulsions, cancer,
skin diseases and gonorrhoea.26,85 Previous chemical studies of
this plant and other Euclea species revealed the presence of
naphthoquinones, triterpenes and avonoids.160–162 Mebe et al.
isolated the new triterpenoid; 3b-(5-hydroxyferuloyl)-Lup20(30)-ene (83) with some of the known compounsds lupene
(84), 7-methyljuglone (85), lupeol (69) and betulin (86) from the
chloroform extract of this plant.163 The isolated compounds
were tested for their cytotoxic activity (ED50 < 20 mg mL 1)
against a panel of cell lines using cell culture systems as
described.164 The results indicate that, the new compound 83
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and compound 85 displayed cytotoxic activity, while the other
compounds were classed as being inactive. Compound 85 was
cytotoxic against all cell lines and its most intense responses
were observed with KB (human nasopharyngeal carcinoma),
P-388 (murine lymphocytic leukemia), LNCaP (human prostate
cancer), ZR-75-1 (human breast cancer) and U373 (human
glioblastoma) cells at 4.8, 0.1, 0.8, 2.2 and 2.7 mg mL 1,
respectively. But, compound 83 was selective, and only showed
activity against two cell lines: P-388 and ZR-75-1 at 2.1 and
4.2 mg mL 1, respectively. Thus the cytotoxic activities of the
isolates correlate with the ethnobotanical use of this plant.
Euclea undulata (Ebenaceae) is used by traditional healers in
the Venda area, Limpopo Province in the treatment of diabetes.
Previous chemical investigation revealed that naphthoquinones
have been isolated from the root, stem and fruit of this plant by
van der Vyver and Gerritsma.165,166 Deutschländer et al. isolated
Fig. 9
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a new triterpene, a-amyrin-3-O-b-(5-hydroxy) ferulic acid (87), in
addition to some of the known compounds; lupeol (69) and
betulin (86) from the crude acetone extract of the root bark of
this plant.167 The isolated compounds were evaluated for, their
hypoglycaemic activities by executing in vitro assays on C2C12
myocytes, as well as their ability to inhibit the carbohydrate
hydrolising enzyme a-glucosidase.168 The in vitro results on
C2C12 myocytes showed that compound 87 has the ability to
inhibit a-glucosidase at a concentration of 200.00 mg mL 1 with
an IC50 value of 4.79 mg mL 1 that correlates with that of the
positive control acarbose with an IC50 value 4.75 mg mL 1. This
study validates the ethnomedicinal use of this plant used by
traditional healers for the treatment of diabetes (Fig. 9).
The nutritive value of Eragrostis species (Poaceae) has been
reported in literature.107,108 Sebastião et al. isolated the known
triterpenoids 3b-(300 ,400 -dihydroxy)-(E)-cinnamoyloxylup-20(29)-
Chemical structures of triterpenoids from Southern African flora (87–95).
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Fig. 10 Chemical structures of a triterpenoids from Southern African flora (96–101).
ene (88) in addition to other compounds from the toluene and
dichloromethane extracts of aerial parts of Eragrostis viscose.109
The genotoxicity of the compounds isolated from this plant was
studied using a cytokinesis-block micronucleus assay and the
Ames test was also used to assess mutagenicity. The results
revealed that compound 88 was cytotoxic including other
compounds from this plant.
Extract from Cassipourea lanceolata (Rhizophoraceae)
showed weak antiproliferative activity when tested against the
A2780 human ovarian cancer cell line and had an IC50 value of
17 mg mL 1. Hou et al. isolated the three new euphane triterpenoids; 1b,3b,11a,26-tetrahydroxy-7,24E-euphadiene (89),
3b,26-dihydroxy-8,24E-euphadien-11-one (90) and (24S)1b,3b,24,25-tetrahydroxy-7,9(11)-euphadiene (91) from the
ethanol extract of the leaves and fruit of this plant collected
from Madagascar.169 The isolated compounds were tested using
the A2780 ovarian cancer cell line assay as described.159 The
compounds 89–91 showed weak antiproliferative activities with
IC50 values of 25, 25, and 32 mM, respectively. Compound 89 was
found to have IC50 values >5 mM when tested against the BT-549
and MCF-7 breast cancer, DU 145 prostate cancer, NCI-H460
and H522-T1 NSCLC, HCC-2998 and HT-29 colon cancer,
OVCAR-5 ovarian cancer, SF-539 CNS cancer, SR and U937
lymphoma, and UACC-257 and MDA-MB-435 melanoma cell
lines. The weak antiproliferative activity of the extract can be
due to masking or other compounds not isolated in this study.
Garcinia goudotiana (Clusiaceae) is used traditionally for its
antiparasitic, antitussive and antimicrobial properties. The
crude acetonic extract in addition to its dichloromethane and
ethyl acetate partitions showed a selective moderate to high
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antimicrobial activity (100 mg mL 1 < MIC < 500 mg mg mL 1 or
MIC # 100 mg mL 1) against Gram-positive bacteria, in particular against three strains of Enteroccocus, six strains of Staphyloccocus and M. smegmatis, in addition to the yeast Candida
albicans.170 Bioassay-guided fractionation of the crude acetonic
extract of the leaves of this plant led to the isolation of two new
prenylated benzoylphloroglucinol derivatives, in addition to a
known xanthone and the known triterpenoid friedelin (92).171
Human colon carcinoma HT29 and human fetal lung broblast
MRC5 cells was also used to evaluate the cytotoxic activities of
the extracts and isolated compounds. The prenylated
compounds showed a high antimicrobial activity against some
Gram-positive bacteria with a moderate cytotoxicity while the
activity of compound 92 was not reported.
The Pittosporum is the only genus of the Pittosporaceae
family found in Malagasy ora.172 Some of the species are used
in traditional medicine as anti-inammatory, antimicrobial and
antispasmodic agents.173 In the search for biologically active
triterpenoids saponins from Pittosporaceae,174 phytochemical
investigation of the ethanol extract from the root barks of
Pittosporum verticillatum (Pittosporaceae) led to the isolation of
three new triterpene saponins, 3-O-[b-D-glucopyranosyl-(1/2)][a-L-arabinopyranosyl-(1/3)]-[a-L-arabinofuranosyl-(1/4)]-bD-glucuronopyranosyl-21-O-(2-acetoxy-2-methylbutanoyl)-R1-barrigenol (93), 3-O-[b-D-glucopyranosyl-(1/2)]-[a-L-arabinopyranosyl-(1/3)]-[a-L-arabinofuranosyl-(1/4)]-b-D-glucuronopyranosyl-21-O-(2-acetoxy-2-methylbutanoyl)-28-O-acetyl-R1-barrigenol (94), 3-O-[b-D-glucopyranosyl-(1/2)]-[a-L-arabinopyranosyl(1/3)]-[a-L-arabinofuranosyl-(1/4)]-b-D-glucuronopyra-nosyl21-O-b,b-dimethylacryloyl-22-O-angeloyl-R1-barrigenol (95) and
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senaciapittoside B (96) (Fig. 10).175 Saponins have been reported
to possess cytotoxic activity.176,177 Thus, the isolated compounds
93–96 were tested for cytotoxicity against one human cancer cell
line, SW480 (colorectal adenocarcinoma), and one embryonic
heart-derived cell line H9c2 (rat cardiomyoblast), using the XTT
method as described.178 Doxorubicin (IC50 1.00 mM on SW480
and 0.50 mM on H9c2) and methotrexate (IC50 N 20.00 mM on
SW480 and 5.00 mM on H9c2) were used as positive controls.
The result showed that, compound 95 exhibited a moderate
cytotoxicity on SW480 cell line, which was however higher than
the positive control methotrexate, whereas a weak activity was
observed on the H9c2 cell line. Compounds 93, 94 and 96 were
found to be inactive on both cell types. All the isolated
compounds 93–96 were inactive in comparison with the positive
control doxorubicin. The results displayed a marginal
RSC Advances
cytotoxicity of triterpenoids saponins of this plant as previously
reported for the structural analog of compound 95 isolated from
Pittosporum viridifolium.179
Polycarpaea corymbosa (Caryophyllaceae) is a cosmopolite
species, that has been recently studied and the results revealed
hepatoprotective activity aer administration of the whole plant
extract to mammals.180,181 This plant has wide applications in
traditional medicine in some part of the world. It is used to treat
cough in traditional Chinese medicine,182 the leaves are used in
Indian to treat inammatory swellings and jaundice.183 Previous
chemical investigation of this plant revealed the presence of
triterpenes, steriods184 and avonoids.183 In the search for biologically active triterpenoid saponins from the Caryophyllaceae
family.185,186 Mahenina et al. isolated four new triterpenoids
saponins (97–100) and a known triterpenoid saponins
Fig. 11 Chemical structures of a sesquiterpene and triterpenoids from Southern African flora (105–117).
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(101) from the methanolic extracts of leaves and roots of this
plant.187 The compounds were 3b-O-(b-D-xylopyranosyl-(1/2)b-D-glucopyranosyl-(1/4)-[b-D-glucopyranosyl-(1/2)]-a-L-arabinopyranosyl)-13b,28-epoxyolean-11-en-16a-ol (97), 3b-O-(b-D-xylopyranosyl-(1/2)-b-D-glucopyranosyl-(1/4)-[b-D-glucopyranosyl(1/2)]-a-L-arabinopyranosyl)-oleana-11,13(18)-diene-16a,28diol (98), 3b-O-(b-D-xylopyranosyl-(1/2)-b-D-glucopyranosyl(1/4)-[b-D-glucopyranosyl-(1/2)]-a-L-arabinopyranosyl)-camelliagenin A (99),16a,22a-diacetoxy-3b-O-(b-D-xylopyranosyl(1/2)-b-D-glucopyranosyl-(1/4)-[b-D-gluco-pyranosyl-(1/2)]a-L-arabinopyranosyl)-olean-12-en-28-ol (100) and apoanagallosaponin IV (101). Triterpenoid saponins have been known to
possess cytotoxic activity.176,177 Thus, the isolated compounds
97, 99–101 were evaluated for their cytotoxic activities against
two human cancer cell lines (colorectal SW480, and prostate
DU145), and one mouse tumour cell line (mammary EMT6)
using a XTT assay.178 The results showed that compound 97 was
the most active compound exhibiting cytotoxicity against these
cell lines with IC50 values ranging from 4.61 to 22.61 mM. This
activity level was greater than that of the anticancer drug, etoposide, which was used as positive control. Compounds 99–101
were inactive (IC50 > 10 mM). Compound 98 was tested only
against the SW480 cell line and an embryonic rat heart-derived
cell line (cardiomyoblast H9c2) by a XTT assay, and was inactive
(IC50 > 10 mM).
Croton pseudopulchellus (Euphorbiaceae) commonly known
as the Small Lavender Croton is used in the coastal area of
Kenya and other parts of Africa to treat various ailments.57,120–124
Langat et al. isolated two new ent-kauren-19-oic acid derivatives;
compounds 50–51 together with the known compounds; 52–55,
60, eudesm-4(15)-ene-1b,6a-diol (102), ( )-7-epivaleran-4-one
(103), germacra-4(15),5E,10(14)-trien-9b-ol (104) and acetyl
aleuritolic acid (105) from the hexane and methylene chloride
extracts of the stem bark of this plant.125 Quantitative assessment of anti-plasmodial activity in vitro was determined via the
parasite lactate dehydrogenase assay using a modied method
described by Makler et al.126 The activity of some of the
compounds was not reported in this study (Fig. 11).
Sutherlandia humilis (Fabaceae) commonly known as cancer
bush is used traditionally for a myriad of indications, ranging
from poor appetite to the prevention and treatment of
cancer.188–190 Analysis of the methanolic leaf extract of this plant
using thin layer chromatography (TLC) revealed the presence of
the triterpenoids sutherlandiosides A (106) and Sutherlandiosides B (107).191 Denise et al. also isolated the new cycloartanetype triterpene glycoside 24,25-O-b-D-diglucopyranosyl-6ahydroxycycloart-3-one (SU3) (108) as the major compound in
this plant.192
Phyllanthus polyanthus (Phyllanthaceae) also known as Forest
Potato-bush is a rare species of plant in South Africa.193 A similar
species of this plant P. delpyanus decocotions of the roots are
used by the Digo of Kenya in the treatment of sexually transmitted diseases.194 Ndlebe et al. isolated two new triterpenoids
phyllanthol (109), phyllanthone (110) in addition to the known
compounds
(20S)-3b-acetoxy-24-methylenedammaran-20-ol
(111), and (20S)-3a-acetoxy-24-methylenedammaran-20-ol (112),
lupenone (113), d-amyrin acetate (114) from the stem bark and
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leaves of this plant.195 Compounds 109–110 has not been isolated
previously from a natural source but have been synthesised.196–200
An ethonobotanical survey of medicinal plants revealed the
wide application of Mimusops obtusifolia (Sapotaceae) in the
management of malaria in Zulu traditional medicine.201 Crude
extracts from the stem bark of this plant showed an in vitro antiplasmodial activity against a CQS of Plasmodium falciparum
(D10) with an IC50 value of 32.5 mg mL 1. Mthokozisi et al. isolated the known triterpenoids taraxerol (115) and sawamilletin
(116) from the stem bark of this plant.202 Quantitative assessment of anti-plasmodial activity in vitro was determined.126 The
results showed that the compounds had IC50 > 100 mg mL 1.
Mthokozisi et al. isolated the triterpenoid ursolic acid (117)
from the leaves of Mimusops caffra (Sapotaceae) collected from
Durban, KwaZulu-Natal Province, South Africa.202,203 This plant
is used in traditional medicine because of its healing properties
against sores and wounds.204 Several triterpenoids isolated from
plants have been reported in literature to demonstrate both in
vitro and in vivo anti-plasmodial activity.205–207 Compound 117
has been previously reported to possess anti-plasmodial
activity.208 and in this study the compound showed an appreciable anti-plasmodial activity with an IC50 value of 6.8 mg mL 1
at the tested concentration using CQS of P. falciparum. The
lower activity of the compound as compared to the crude extract
could be due to synergistic effect with other compounds,
decomposition during fractionation.
Morus nigra (Moraceae) also known as black mulberry
extracts have been reported to have antibacterial and fungicidal
activity.209 This plant is used economically for sericulture, as a
feed for the domesticated silkworm, the bark of this plant is
being used to expel tape worm. Mazimba et al. isolated the
known compounds 62 and 63 in addition to other compounds
from the stem bark of this plant.70,137,210
4 Conclusions
In this review, we present an overview of the results of biological
activities of selected NPs (alkaloids and terpenoids) isolated
from plants used in traditional medicine in Sothern Africa
(covering 10 countries). Our focus has been on plants whose
ethnobotanical uses correlate with the biological activities of
the derived NPs. The plant sources, geographical collection sites
and chemical structures of pure compounds were retrieved
from literature sources comprising data collected from articles
from major NP peer reviewed journals, spanning the period
1971 to 2014. Thus, the report does not claim to be exhaustive.
However, the goal has been to document the baseline knowledge and lay the foundation for subsequent investigations. Our
survey consisted in collecting data from the literature sources,
mainly from MSc and PhD theses from university libraries
within the region. We also used the author queries in major
natural product and medicinal chemistry journals. The
collected data includes plant sources, uses of plant material in
traditional medicine, plant families, region of collection of
plant material, isolated metabolites and type (e.g. avonoid,
terpenoid, etc.), measured biological activities of isolated
compounds (as commented in the literature). The aim of this
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study has been to provide a survey of the biological activities of
compounds derived from Southern African ora versus the
ethnobotanical uses of the plant species from which the
compounds have been isolated. This series of reviews, dedicated to Southern African ora, was intended to give an in depth
coverage of the chemotaxonomy of Southern African ora and a
cheminformatics analysis of the derived natural products. In
this study, a literature survey led to the collection of 864
secondary metabolites from 101 plant species from 57 plant
families. A correlation between the known biological activities
of isolated compounds and the ethnobotanical uses of the
plants has been attempted. From the data presented in
Tables 1–6, the biological activities of 62 out of the 117 plant
metabolites commented in the text could be used to validate the
ethnobotanical uses of the plant species. Even though some of
the biological activies don't look famous, the aforementioned
activities could be further ne-tuned by chemical modications. Moreover, virtual screening methods could be used to
enhance drug discovery by docking some of the compounds
towards specic drug target sites and chemically modifying the
NPs, so as to improve binding to the target site. This rst part
rather focuses of alkaloids and terpenoids. The other
compound classes will be examined subsequently.
Acknowledgements
Financial support is acknowledged from Lhasa Ltd, Leeds, UK
through the Chemical and Bioactivity Information Centre
(CBIC), University of Buea, Cameroon. Ms. Irene N. Mukoko
(Department of Chemistry, University of Buea) assisted in the
data analysis. FNK acknowledges a Georg Forster fellowship for
postdoctoral researchers from the Alexander von Humboldt
Foundation.
Notes and references
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4 S. M. N. Efange, Natural products: a continuing source of
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5 World Health Organization, Traditional traditional
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6 World Health Organization, WHO traditional medicine
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7 F. Ntie-Kang, L. L. Lifongo, L. M. Mbaze, N. Ekwelle,
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9 R. M. Cowling and C. Hilton-Taylor, Phytogeography, ora
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