By interchanging the order of reactions, two types of skeletons were created and a neuroactive ar... more By interchanging the order of reactions, two types of skeletons were created and a neuroactive artificial glutamate analog was developed.
Herein we report stereoselective generation of two skeletons, 1,3-dioxane and tetrahydropyranol, ... more Herein we report stereoselective generation of two skeletons, 1,3-dioxane and tetrahydropyranol, by oxa-Michael reaction as the key reaction from d-hydroxyenone. The construction of the 1,3-dioxane skeleton, achieved through hemiacetal formation followed by oxa-Michael reaction from d-hydroxyenone, was exploited to access structurally diverse heterotricyclic artificial glutamate analogs. On the other hand, formation of a novel tetrahydro-2H-pyranol skeleton was accomplished by the inverse reaction order: oxa-Michael reaction followed by hemiacetal formation. Thus, this study succeeded in showing that structural diversity in a compound collection can be acquired by interchanging the order of just two reactions. Among the skeletally diverse, heterotricyclic artificial glutamate analogs synthesized in this study, a neuronally active compound named TKM-50 was discovered in the mice in vivo assay.
Background: The high mortality rate due to infectious diseases has recently been associated with ... more Background: The high mortality rate due to infectious diseases has recently been associated with the development of resistance to antibiotics by several strains of microorganisms worldwide. One of the pathophysiological conditions of mammalian tissues in response to infectious organisms is oxidative stress. Natural extracts or their chemical constituents as antioxidants are known to be very effective at preventing the destructive processes caused by oxidative stress. The main aim of the current study was to evaluate in vitro antibacterial, antioxidant, and cytotoxic effects of ethanolic root extracts of Kedrostis capensis A. Meeuse (Cucurbitaceae) and Trachyandra asperata Kunth. (Xanthorrhoeaceae). Materials and Methods: The assessments of antibacterial and antioxidant effects were performed using well diffusion method and 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging activity assay, respectively, while cytotoxic potentials were evaluated by employing the brine shrimp toxicity model. Results: K. capensis extract possessed bactericidal activity against Escherichia coli and Staphylococcus aureus and bacteriostatic activity against Pseudomonas aeruginosa with minimum inhibition concentration (MIC) values ranging from 62.5 to 500 µm/mL and minimum bactericidal concentration (MBC) values varying from 125 to 1000 µm/mL, while T. asperata extract was only bacteriostatic against S. aureus with MIC value of 500 µm/mL and MBC value greater than 1000 µm/mL. Both K. capensis and T. asperata extracts scavenged DPPH free radicals in a concentration-dependent manner with the half maximal inhibitory concentration (IC 50) values of 113.68 ± 0.11 µg/mL and 134.63 ± 0.27 µg/mL, respectively. K. capensis extract exhibited a relatively higher toxicity potential with 50% lethality concentration (LC 50) value of 102.37 ± 0.19 µg/mL, while T. asperata was non-toxic with lower LC 50 value of 522.75 ± 0.35 µg/mL. Obtained results suggest that K. capensis and T. asperata ethanolic root extracts possess bioactive secondary metabolites with antibacterial, antioxidant, and cytotoxicity properties with potential pharmaceutical applications.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
International Journal of Pharmacy and Chemistry, 2021
The majority of the populations, both from developed and developing countries, use herbal prepara... more The majority of the populations, both from developed and developing countries, use herbal preparations for primary healthcare purposes. In particular, the use of herbal preparations in Lesotho is high due to inadequate healthcare facilities and inaccessibility of healthcare services. Herbal preparations are inexpensive, easily accessible and culturally accepted than conventional medicines. Although herbal preparations are popularly used, they could be contaminated with pathogenic microbes, toxic heavy metals and non-metals, agrochemical residues, mycotoxins and endotoxins and, thus World Health Organization (WHO) recommends that herbal preparations should be evaluated for safety, efficacy and potency so as to protect the consumers. This study was, therefore, designed to evaluate heavy metals and microbial contaminants in some of the commercially available herbal preparations in Maseru, Lesotho. A total of five herbal preparations were randomly purchased from different areas of Maser...
Herein we report stereoselective formation of 1,3-dioxanes by oxa-Michael reaction of cis-arrange... more Herein we report stereoselective formation of 1,3-dioxanes by oxa-Michael reaction of cis-arranged δ-siloxyenones using 1,3,5-trioxane and methanesulfonic acid (MsOH). The yields were satisfactoril...
In this study, the antioxidant activity and phytochemical analysis of dichloromethane (DCM) and m... more In this study, the antioxidant activity and phytochemical analysis of dichloromethane (DCM) and methanolic extracts of Pseudognaphalium undulatum (L.) Hillard & B.L Burtt were evaluated using 2,2diphenyl-1-picrylhydrazyl (DPPH) assay, hydrogen peroxide (H2O2) assay, ferric reducing power assay and standard analytical methods. Out of nine phytochemical classes determined, the DCM extract showed the presence of 33.3% of them while the methanolic extract showed the presence of 88.9%. The extracts showed significant antioxidant properties of which the methanolic extract showed the DPPH and H2O2 IC50 values of 706.38 and <50 µg/ml, respectively. Similarly, the methanolic extract showed the highest total phenolic and flavonoid contents of 213.03±0.82 mg GAE/g DW and 43.81±0.93 mg QE/g DW, respectively. The ferric reducing powers of both extracts showed a linear correlation with the ascorbate standard. Further studies such as bio-guided fractionation are required to explore in depth the pharmacological and ethnomedicinal properties of pure compounds from this plant.
In this study, the antioxidant activity and phytochemical analysis of dichloromethane (DCM) and m... more In this study, the antioxidant activity and phytochemical analysis of dichloromethane (DCM) and methanolic extracts of Pseudognaphalium undulatum (L.) Hillard & B.L Burtt were evaluated using 2,2diphenyl-1-picrylhydrazyl (DPPH) assay, hydrogen peroxide (H2O2) assay, ferric reducing power assay and standard analytical methods. Out of nine phytochemical classes determined, the DCM extract showed the presence of 33.3% of them while the methanolic extract showed the presence of 88.9%. The extracts showed significant antioxidant properties of which the methanolic extract showed the DPPH and H2O2 IC50 values of 706.38 and <50 µg/ml, respectively. Similarly, the methanolic extract showed the highest total phenolic and flavonoid contents of 213.03±0.82 mg GAE/g DW and 43.81±0.93 mg QE/g DW, respectively. The ferric reducing powers of both extracts showed a linear correlation with the ascorbate standard. Further studies such as bio-guided fractionation are required to explore in depth the...
Lesotho has a rich supply of indigenous medicinal plant resources. More than a dozen Lesotho medi... more Lesotho has a rich supply of indigenous medicinal plant resources. More than a dozen Lesotho medicinal plants have been used to treat minor wound infections among Basotho for over 100 years. The aim is to provide scientific validation of their antimicrobial activities against microorganisms relevant to the skin. The anti-infective activities of plants are thought to be due to the presence of active phytochemicals in parts of the plants, especially phenolic compounds, anthraquinones, glycosides, and alkaloids. Although there is limited research that establishes the structure-activity relationship of those phytochemicals, there are reports that attributed the phytochemical constituents with the antimicrobial effects through a variety of mechanisms ranging from inhibition of cytoplasmic membrane function, inhibition of energy metabolism to inhibition of bacterial nucleic acid synthesis. The role of the pharmacist is to provide medical information on these compounds to promote the safe use of herbal products and in combination with conventional medicines.
Infections associated with multidrug resistant organisms result in increased morbidity and mortal... more Infections associated with multidrug resistant organisms result in increased morbidity and mortality in Lesotho and globally, thus, there is immediate need to discover new antibiotics against resistant bacteria through systematic examination of inexpensive local herbs. Here, we report for the first time, the well-defined and publicly available prototype library that consists of 20 different crude extracts derived from crude drug samples of medicinal plants of Lesotho used for treatment of infectious diseases. We also described the coupling of soxhlet extraction with liquid-liquid fractionation to give partially refined organic and aqueous extracts, and disclose that the extracts from the leaves and whole plant contained about twice as much organic soluble phytochemicals as aqueous soluble phytoconstituents. While the roots and bark contained about 2 and 5 times more of aqueous soluble than organic soluble phytochemicals respectively, especially when extracting with 90% ethanol. The library represents the potential phytochemicals in herbal prescriptions dispensed by traditional healers in Lesotho. The extracts are publicly available upon request through the corresponding author and efforts to expand the library are still continuing. This methodology could be followed to develop other libraries. Introduction The issue of antibiotic resistance is the universal concern, thus, there is immediate need to discover new antibiotics against resistant bacteria through systematic exploration of inexpensive local herbs [1]. According to Tim Cushnie et al., [2] frequently encountered conventional antibiotics in clinical setting, such as β-lactams, aminoglycosides, tetracyclines and macrolides were discovered through systematic examination of traditional natural products and associated traditional knowledge. Even though the indigenous communities such as Basotho relied on traditional medicinal herbs for the treatment of infectious disease since time immemorial [3] new antibiotic discoveries from medicinal plants are especially rare possibly due to an over-reliance on synthetic chemical libraries. Well-defined and publicly-available libraries of crude extracts from crude drugs of plant origin are needed for the advancement of new antibiotic drug discovery research from traditional plants [4]. Plants are often described as the massive storage of pharmacologically active chemical compounds (soluble phytochemicals) that are obtained through the extraction process [5] Optimum extraction yields have been reported when extracting with aqueous organic solvents than their respective absolute organic solvent as well as by using a refluxing extraction technique [6]. Also, a more refined plant extraction procedure needs to be followed to produce relatively refined extract samples for stronger zones of inhibition [7] Our laboratory have been paying attention to developing a practical extraction technique that gives partially purified crude extracts from crude drugs. In this paper, we attempt to setup a pilot library composed of partially refined crude extracts from indigenous medicinal plants of Lesotho with antimicrobial properties [3]. We also described the coupling of soxhlet extractor with liquid-liquid extraction, the methodology used to generate the library. Finally, we compare the effects of using 90% acetone and 90% ethanol on extraction yields of individual crude drugs.
By interchanging the order of reactions, two types of skeletons were created and a neuroactive ar... more By interchanging the order of reactions, two types of skeletons were created and a neuroactive artificial glutamate analog was developed.
Herein we report stereoselective generation of two skeletons, 1,3-dioxane and tetrahydropyranol, ... more Herein we report stereoselective generation of two skeletons, 1,3-dioxane and tetrahydropyranol, by oxa-Michael reaction as the key reaction from d-hydroxyenone. The construction of the 1,3-dioxane skeleton, achieved through hemiacetal formation followed by oxa-Michael reaction from d-hydroxyenone, was exploited to access structurally diverse heterotricyclic artificial glutamate analogs. On the other hand, formation of a novel tetrahydro-2H-pyranol skeleton was accomplished by the inverse reaction order: oxa-Michael reaction followed by hemiacetal formation. Thus, this study succeeded in showing that structural diversity in a compound collection can be acquired by interchanging the order of just two reactions. Among the skeletally diverse, heterotricyclic artificial glutamate analogs synthesized in this study, a neuronally active compound named TKM-50 was discovered in the mice in vivo assay.
Background: The high mortality rate due to infectious diseases has recently been associated with ... more Background: The high mortality rate due to infectious diseases has recently been associated with the development of resistance to antibiotics by several strains of microorganisms worldwide. One of the pathophysiological conditions of mammalian tissues in response to infectious organisms is oxidative stress. Natural extracts or their chemical constituents as antioxidants are known to be very effective at preventing the destructive processes caused by oxidative stress. The main aim of the current study was to evaluate in vitro antibacterial, antioxidant, and cytotoxic effects of ethanolic root extracts of Kedrostis capensis A. Meeuse (Cucurbitaceae) and Trachyandra asperata Kunth. (Xanthorrhoeaceae). Materials and Methods: The assessments of antibacterial and antioxidant effects were performed using well diffusion method and 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging activity assay, respectively, while cytotoxic potentials were evaluated by employing the brine shrimp toxicity model. Results: K. capensis extract possessed bactericidal activity against Escherichia coli and Staphylococcus aureus and bacteriostatic activity against Pseudomonas aeruginosa with minimum inhibition concentration (MIC) values ranging from 62.5 to 500 µm/mL and minimum bactericidal concentration (MBC) values varying from 125 to 1000 µm/mL, while T. asperata extract was only bacteriostatic against S. aureus with MIC value of 500 µm/mL and MBC value greater than 1000 µm/mL. Both K. capensis and T. asperata extracts scavenged DPPH free radicals in a concentration-dependent manner with the half maximal inhibitory concentration (IC 50) values of 113.68 ± 0.11 µg/mL and 134.63 ± 0.27 µg/mL, respectively. K. capensis extract exhibited a relatively higher toxicity potential with 50% lethality concentration (LC 50) value of 102.37 ± 0.19 µg/mL, while T. asperata was non-toxic with lower LC 50 value of 522.75 ± 0.35 µg/mL. Obtained results suggest that K. capensis and T. asperata ethanolic root extracts possess bioactive secondary metabolites with antibacterial, antioxidant, and cytotoxicity properties with potential pharmaceutical applications.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
International Journal of Pharmacy and Chemistry, 2021
The majority of the populations, both from developed and developing countries, use herbal prepara... more The majority of the populations, both from developed and developing countries, use herbal preparations for primary healthcare purposes. In particular, the use of herbal preparations in Lesotho is high due to inadequate healthcare facilities and inaccessibility of healthcare services. Herbal preparations are inexpensive, easily accessible and culturally accepted than conventional medicines. Although herbal preparations are popularly used, they could be contaminated with pathogenic microbes, toxic heavy metals and non-metals, agrochemical residues, mycotoxins and endotoxins and, thus World Health Organization (WHO) recommends that herbal preparations should be evaluated for safety, efficacy and potency so as to protect the consumers. This study was, therefore, designed to evaluate heavy metals and microbial contaminants in some of the commercially available herbal preparations in Maseru, Lesotho. A total of five herbal preparations were randomly purchased from different areas of Maser...
Herein we report stereoselective formation of 1,3-dioxanes by oxa-Michael reaction of cis-arrange... more Herein we report stereoselective formation of 1,3-dioxanes by oxa-Michael reaction of cis-arranged δ-siloxyenones using 1,3,5-trioxane and methanesulfonic acid (MsOH). The yields were satisfactoril...
In this study, the antioxidant activity and phytochemical analysis of dichloromethane (DCM) and m... more In this study, the antioxidant activity and phytochemical analysis of dichloromethane (DCM) and methanolic extracts of Pseudognaphalium undulatum (L.) Hillard &amp; B.L Burtt were evaluated using 2,2diphenyl-1-picrylhydrazyl (DPPH) assay, hydrogen peroxide (H2O2) assay, ferric reducing power assay and standard analytical methods. Out of nine phytochemical classes determined, the DCM extract showed the presence of 33.3% of them while the methanolic extract showed the presence of 88.9%. The extracts showed significant antioxidant properties of which the methanolic extract showed the DPPH and H2O2 IC50 values of 706.38 and &lt;50 µg/ml, respectively. Similarly, the methanolic extract showed the highest total phenolic and flavonoid contents of 213.03±0.82 mg GAE/g DW and 43.81±0.93 mg QE/g DW, respectively. The ferric reducing powers of both extracts showed a linear correlation with the ascorbate standard. Further studies such as bio-guided fractionation are required to explore in depth the pharmacological and ethnomedicinal properties of pure compounds from this plant.
In this study, the antioxidant activity and phytochemical analysis of dichloromethane (DCM) and m... more In this study, the antioxidant activity and phytochemical analysis of dichloromethane (DCM) and methanolic extracts of Pseudognaphalium undulatum (L.) Hillard & B.L Burtt were evaluated using 2,2diphenyl-1-picrylhydrazyl (DPPH) assay, hydrogen peroxide (H2O2) assay, ferric reducing power assay and standard analytical methods. Out of nine phytochemical classes determined, the DCM extract showed the presence of 33.3% of them while the methanolic extract showed the presence of 88.9%. The extracts showed significant antioxidant properties of which the methanolic extract showed the DPPH and H2O2 IC50 values of 706.38 and <50 µg/ml, respectively. Similarly, the methanolic extract showed the highest total phenolic and flavonoid contents of 213.03±0.82 mg GAE/g DW and 43.81±0.93 mg QE/g DW, respectively. The ferric reducing powers of both extracts showed a linear correlation with the ascorbate standard. Further studies such as bio-guided fractionation are required to explore in depth the...
Lesotho has a rich supply of indigenous medicinal plant resources. More than a dozen Lesotho medi... more Lesotho has a rich supply of indigenous medicinal plant resources. More than a dozen Lesotho medicinal plants have been used to treat minor wound infections among Basotho for over 100 years. The aim is to provide scientific validation of their antimicrobial activities against microorganisms relevant to the skin. The anti-infective activities of plants are thought to be due to the presence of active phytochemicals in parts of the plants, especially phenolic compounds, anthraquinones, glycosides, and alkaloids. Although there is limited research that establishes the structure-activity relationship of those phytochemicals, there are reports that attributed the phytochemical constituents with the antimicrobial effects through a variety of mechanisms ranging from inhibition of cytoplasmic membrane function, inhibition of energy metabolism to inhibition of bacterial nucleic acid synthesis. The role of the pharmacist is to provide medical information on these compounds to promote the safe use of herbal products and in combination with conventional medicines.
Infections associated with multidrug resistant organisms result in increased morbidity and mortal... more Infections associated with multidrug resistant organisms result in increased morbidity and mortality in Lesotho and globally, thus, there is immediate need to discover new antibiotics against resistant bacteria through systematic examination of inexpensive local herbs. Here, we report for the first time, the well-defined and publicly available prototype library that consists of 20 different crude extracts derived from crude drug samples of medicinal plants of Lesotho used for treatment of infectious diseases. We also described the coupling of soxhlet extraction with liquid-liquid fractionation to give partially refined organic and aqueous extracts, and disclose that the extracts from the leaves and whole plant contained about twice as much organic soluble phytochemicals as aqueous soluble phytoconstituents. While the roots and bark contained about 2 and 5 times more of aqueous soluble than organic soluble phytochemicals respectively, especially when extracting with 90% ethanol. The library represents the potential phytochemicals in herbal prescriptions dispensed by traditional healers in Lesotho. The extracts are publicly available upon request through the corresponding author and efforts to expand the library are still continuing. This methodology could be followed to develop other libraries. Introduction The issue of antibiotic resistance is the universal concern, thus, there is immediate need to discover new antibiotics against resistant bacteria through systematic exploration of inexpensive local herbs [1]. According to Tim Cushnie et al., [2] frequently encountered conventional antibiotics in clinical setting, such as β-lactams, aminoglycosides, tetracyclines and macrolides were discovered through systematic examination of traditional natural products and associated traditional knowledge. Even though the indigenous communities such as Basotho relied on traditional medicinal herbs for the treatment of infectious disease since time immemorial [3] new antibiotic discoveries from medicinal plants are especially rare possibly due to an over-reliance on synthetic chemical libraries. Well-defined and publicly-available libraries of crude extracts from crude drugs of plant origin are needed for the advancement of new antibiotic drug discovery research from traditional plants [4]. Plants are often described as the massive storage of pharmacologically active chemical compounds (soluble phytochemicals) that are obtained through the extraction process [5] Optimum extraction yields have been reported when extracting with aqueous organic solvents than their respective absolute organic solvent as well as by using a refluxing extraction technique [6]. Also, a more refined plant extraction procedure needs to be followed to produce relatively refined extract samples for stronger zones of inhibition [7] Our laboratory have been paying attention to developing a practical extraction technique that gives partially purified crude extracts from crude drugs. In this paper, we attempt to setup a pilot library composed of partially refined crude extracts from indigenous medicinal plants of Lesotho with antimicrobial properties [3]. We also described the coupling of soxhlet extractor with liquid-liquid extraction, the methodology used to generate the library. Finally, we compare the effects of using 90% acetone and 90% ethanol on extraction yields of individual crude drugs.
Tetrahydropyrans are important class of compounds that occur as building blocks in many biologica... more Tetrahydropyrans are important class of compounds that occur as building blocks in many biologically active natural products. [1] The coupling of homoallylic alcohols with aldehyde in the presence of acid catalyst, known as Prins cyclization, has been reported to produce large number of tetrahydropyran derivatives. [2] Prins cyclization of 1,3,5-trioxane and homoallylic alcohol for cis-fused tetrahydropyrans was reported in 2010. [3] Encouraged by that work, we decided to employ Prins strategy using 1,3,5-trioxane as an equivalent for formaldehyde, for construction of the characteristic cis-fused tetrahydropyran motif that can be envisioned as a versatile precursor for analogs of dysiherbaine, the potent agonist for the kainate receptors. [4] When homoallylic alcohol 1 was treated with two equiv of 1,3,5-trioxane and three equiv of methanesulfonic acid in dichloromethane at rt for 18 h, Prins cyclization proceeded smoothly to give corresponding cis-fused tetrahydropyran 2 in 43% yield. Extra one equiv of 1,3,5-trioxane and one equiv methanesulfonic acid were necessarily added to drive the reaction to completion. Structure of the cis-fused tetrahydropyran product was characterized using 1 H NMR spectroscopy.
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minor wound infections among Basotho for over 100 years. The aim is to provide scientific validation of their antimicrobial activities against
microorganisms relevant to the skin. The anti-infective activities of plants are thought to be due to the presence of active phytochemicals
in parts of the plants, especially phenolic compounds, anthraquinones, glycosides, and alkaloids. Although there is limited research that
establishes the structure-activity relationship of those phytochemicals, there are reports that attributed the phytochemical constituents with
the antimicrobial effects through a variety of mechanisms ranging from inhibition of cytoplasmic membrane function, inhibition of energy
metabolism to inhibition of bacterial nucleic acid synthesis. The role of the pharmacist is to provide medical information on these compounds
to promote the safe use of herbal products and in combination with conventional medicines.
minor wound infections among Basotho for over 100 years. The aim is to provide scientific validation of their antimicrobial activities against
microorganisms relevant to the skin. The anti-infective activities of plants are thought to be due to the presence of active phytochemicals
in parts of the plants, especially phenolic compounds, anthraquinones, glycosides, and alkaloids. Although there is limited research that
establishes the structure-activity relationship of those phytochemicals, there are reports that attributed the phytochemical constituents with
the antimicrobial effects through a variety of mechanisms ranging from inhibition of cytoplasmic membrane function, inhibition of energy
metabolism to inhibition of bacterial nucleic acid synthesis. The role of the pharmacist is to provide medical information on these compounds
to promote the safe use of herbal products and in combination with conventional medicines.