PHA 051: Pharmaceutical and Medicinal Chemistry

Module #3 Student Activity Sheet

Name: _________________________________________________________________ Class number: _______

Section: ____________ Schedule: ________________________________________ Date: ________________

LESSON TITLE: BIOCHEMICAL CLASSES OF DRUG TARGETS Materials:

FOR DRUG DISCOVERY AND CHEMOTHERAPEUTIC DRUGS Book, pen and notebook, Periodic Table of
Elements, index card/class list, slide
LEARNING OUTCOMES: presentation.
Upon completion of this lesson, the pharmacy student can:
1. Discussing the processes of targeted-protein mediated drug References:
mechanism. Patrick, Graham L., (2013) An Introduction to
2. Discuss the knowledge on enzymes, receptor, and drug targets Medicinal Chemistry. (5th edition). Oxford:
and its role in drug Pharmacodynamics, Oxford University Press.
3. Demonstrate understanding of the molecular structures of major
macromolecular targets in the body Wilson and Gisvold’s. (2011). Textbook of
4. Explaining the importance of each parameters that affects the Organic Medicinal and Pharmaceutical
drug mechanism of actions in the body. Chemistry. (12th edition). Philadelphia:
5. Discuss different types of chemotherapeutic drugs and it’s clinical Lippincott Williams & Wilkins
uses

A. LESSON PREVIEW/REVIEW
Enumerate different types of intermolecular forced and give examples.
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B. MAIN LESSON (50 minutes)

What is Drug?

Ø Drugs refer to pharmaceutical products that pertain to chemical compounds or biological substances, other than
food, intended for use in the treatment, prevention, or diagnosis of disease in humans or animals, including the following:
(1) Any article recognized in the official USP/NF, Homeopathic Pharmacopeia of the United States of America, Philippine
Pharmacopeia, Philippine National Drug Formulary, British Pharmacopoeia, European Pharmacopoeia, Japanese
Pharmacopoeia, and any official compendium or any supplement to them; (2) Any article intended for use in diagnosis,
cure, mitigation, treatment, or prevention of disease of man or animals; (3) Any article, other than food, intended to affect
the structure or any function of the human body or animals; (4) Any article intended for use, as a component of articles,
specified in clauses (1), (2) and (3), not including devices or their components, parts and accessories; and (5) Herbal or
traditional drugs as defined in Republic Act No. 9502.
Ø Drugs are compounds that interact with a biological system to produce a biological response.
Ø The dose level of a compound determines whether it will act as a medicine or as a poison.
Ø The therapeutic index is a measure of a drug’s beneficial effect at a low dose versus its harmful effects at higher
dose. A high therapeutic index indicates a large safety margin between beneficial and toxic doses.
ENZYMES AS DRUG TARGETS

A. Inhibitors acting on the Active Site of an enzyme

Reversible inhibitors
o Inactivates an enzyme through non-covalent
 PHA 051: Pharmaceutical and Medicinal Chemistry
Module #3 Student Activity Sheet

o More easily reversed interactions.

o Competitive, Uncompetitive and non-competitive inhibitors.

Irreversible inhibitors:
o Inactivates an enzyme by bonding covalently to a particular group at the active site.
o Irreversible
o The most effective irreversible inhibitors are those that contain an electrophilic functional group (X) or
Halides, capable of reacting with a nucleophilic group present on an amino acid side chain. Irreversible
inhibitors can be classified into group-specific reagents, substrate analogs and suicide inhibitors.

Competitive Inhibitors
o Any compound that bears a structural resemblance to a particular substrate and thus competes with that
substrate for binding at the active site of an enzyme.
o The inhibitor is not acted on by the enzyme but does prevent the substrate from approaching the active
site.

B. Inhibitors acting at Allosteric Binding Sites

When an allosteric inhibitor binds to its binding site, the resulting induced fit also deforms the shape of the active
site such that it becomes unrecognizable to the substrate. Drugs can be designed to mimic this natural control of the
enzyme. If the drug binds through intermolecular interactions, the inhibition is reversible. If the drug contains a reactive
group allowing it to form a covalent bond to the allosteric binding site, the inhibition is
irreversible.

The drug 6-mercaptopurine, used in the treatment of leukemia, is an example of

an allosteric inhibitor. It inhibits the first enzyme involved in the synthesis of purines
and blocks purine synthesis. In turn, this blocks DNA synthesis.

C. Uncompetitive and Non-Competitive Inhibitors

Uncompetitive inhibitors
o inhibitor binds to the enzyme–substrate complex. In this situation, increasing the substrate concentration
will not overcome inhibition. Indeed, the level of inhibition is dependent on sufficient substrate being
present to form the enzyme–substrate complex. Therefore, uncompetitive inhibitors are less effective at
low substrate concentrations. Uncompetitive inhibitors are not very common.

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 PHA 051: Pharmaceutical and Medicinal Chemistry
Module #3 Student Activity Sheet

Non-competitive inhibitors

o binds to an allosteric binding site and inhibits the

enzyme-catalyzed reaction without affecting the
strength of substrate binding. This would occur if the
induced fit arising from the binding of the allosteric
inhibitor distorts the active site sufficiently to prevent
the catalytic mechanism, but has no effect on the
substrate binding process.

D. Transition-state Analogues: Renin Inhibitors

A drug should bind more strongly than either the substrate or
the product and be a strong inhibitor as a result.

Renin is a protease enzyme which is

responsible for hydrolyzing a specific peptide
bond in the protein angiotensinogen to form
angiotensin I. Angiotensin I is further
converted to angiotensin II, which acts to
constrict blood vessels and retain fluid in the
kidneys, both of which lead to a rise in blood
pressure. Therefore, an inhibitor of renin
should act as an antihypertensive agent (i.e., lower blood pressure) by preventing the first stage in this process.

E. Suicide Substrates
Suicide substrates is an irreversible form of enzyme inhibition that occurs when an enzyme binds a substrate
analog and forms an irreversible complex with it through a covalent bond during the normal catalysis reaction.
It produces a reactive group that reacts irreversibly to form a stable inhibitor-enzyme complex. This usually
uses a prosthetic group or a coenzyme, forming electrophilic alpha and beta unsaturated carbonyl compounds and
imines.
One example of a suicide substrate is clavulanic acid, which is used clinically in antibacterial medications
(e.g., Augmentin) to inhibit the bacterial β-lactamase enzyme. This enzyme is responsible for the penicillin
resistance observed in several bacterial strains because it catalyzes the hydrolysis of the penicillin β-lactam ring.

F. Isozyme Selectivity Inhibitors

Identification of isozymes that predominate in some tissues, but not others, allows the possibility of
designing tissue-selective enzyme inhibitors.
Cyclooxygenase has two isozymes: COX-1 and COX-2.
• Both isozymes carry out the same reactions
• COX-1 is the isozyme that is active under normal healthy conditions.
• The normally dormant COX-2 becomes activated and produces excess inflammatory prostaglandins. Therefore,
drugs such as Valdecoxib, Rofecoxib, and Celecoxib have been developed to be selective for the COX-2 isozyme,
so that only the production of inflammatory prostaglandins is reduced. Selectivity is possible by taking advantage
of the fact that an isoleucine group is present in the binding site of COX-1, whereas the corresponding group in
COX-2 is valine.

G. Medicinal uses of Enzyme Inhibitors

1. Enzyme inhibitors used against microorganisms
2. Enzyme inhibitors used against viruses
3. Enzyme inhibitors used against the body’s own enzymes

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RECEPTORS AS DRUG TARGETS

Agonists – drugs that occupy receptor and activate them

1. Full Agonist
A full agonist is a drug which is capable
of producing a maximum response that the
target system is capable of.
2. Partial Agonist
Can never achieve the maximal
response that the system is capable of,
because its efficacy is lower than that of full
agonist. Perhaps the partial agonist
occupies all the receptors and interacts with
them in a manner identical to the full
agonist, but for some receptors inexplicably
fails to activate the ligand binding site or
secondary messenger system.
A partial agonist drug is used at the
same time with a full agonist, both acts on
the same receptors, then the partial agonist will act as an antagonist, competing with the full agonist for a
finite number of binding sites. If the binding sites occupied by the partial agonist, some will not be activated,
which reduces the total drug effect.

3. Inverse Agonist
In inverse agonist is a ligand which, by binding to a receptor, produces the opposite of the effect which
would be produced when an agonist binds the same receptor

Antagonist- drugs that occupy receptor but do not activate them. Antagonists block receptor activation by agonist.
1. Silent Antagonist
Aka neutral antagonist; drug that attenuates the effects of agonists, producing a functional reduction in
signal transduction. Affects only ligand-dependent receptor activation and displays no intrinsic activity itself.
2. Competitive Antagonist
A competitive antagonist competes for the same binding site with an agonist, and their binding is mutually
exclusive. Increasing the concentration of agonist can overcome competitive antagonist activity. The potency
of agonist reduced but not the maximum efficacy. The Schild equation describes the potency of a competitive
antagonist in terms of its concentration and its ratio to the concentration of the agonist.
3. Non-Competitive Antagonist
Prevent the action of an agonist without any effect on the binding of the agonist to the receptor.
4. Insurmountable Antagonist

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Module #3 Student Activity Sheet

Can reduce the maximum effect of the agonist, and this inhibitory effect is not affected by increasing
agonist concentration.
5. Irreversible Antagonist
Insurmountable, but does not have to be non-competitive. An example is an antagonist which bind
covalently to the receptor binding site.
6. Physiological Antagonist
Non-competitive, but does not have to be insurmountable. An example is an antagonist which acts
indirectly to depress the physiological parameter which the agonist stimulates.
Desensitization and Sensitization
Desensitization may occur when an agonist is bound to its receptor for a long period of time. Phosphorylation of
the receptor results in a change of conformation.
Sensitization can occur when an antagonist is bound to a receptor for a long period of time. The cell synthesizes
more receptor to counter the antagonist effect.

A. Tolerance and Dependence

Tolerance is a situation where increased doses of a drug are required over time to achieve the same effect.
Dependence is related to the body’s ability to adapt the presence of a drug. On stopping the drug, withdrawal
symptoms occur as a result of abnormal levels of target receptor.

B. Receptor Types and Subtypes

C. Affinity, Efficacy and Potency

Þ Affinity of a drug for a receptor is a measure of how strongly that drug binds to the receptor.
Þ Efficacy is a measure of the maximum biological effect that a drug can produce as a result of receptor
binding.
A compound with high affinity does not necessarily have high efficacy.
Þ Potency of a drug refers to the amount of drug required to achieve a defined biological effect—the smaller
the dose required, the more potent the drug. It is possible for a drug to be potent but have a low efficacy
NUCLEIC ACIDS AS DRUG TARGETS (CHEMOTHERAPY)
Although proteins are the target for the majority of clinically useful drugs, there are many important drugs which
target nucleic acids, especially in the areas of antibacterial and anticancer therapy.

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A. Intercalating Drugs Acting on DNA

Intercalating drugs are compounds that
contain planar or heteroaromatic features
which slip between the base-pair layers of
the DNA double helix.
Proflavine is an example of a group
of antibacterial compounds called the
aminoacridines, which were used during
World Wars I and II to treat deep surface
wounds.

Dactinomycin (previously called actinomycin D) is a

naturally occurring antibiotic that was first isolated from
Streptomyces parvullis in 1953, and was shown to be
an effective anticancer agent in children.
Doxorubicin is one of the most effective anticancer
drugs ever discovered, and belongs to a group of
naturally occurring antibiotics called the
anthracyclines. It was first isolated from Streptomyces
peucetius in 1967 and contains a tetracyclic system
where three of the rings are planar.

Bleomycins are complex natural products that were

isolated from Streptomyces verticillus in 1962 and are some
of the few anticancer drugs not to cause bone marrow
depression. Their structure includes a bithiazole ring system
which intercalates with DNA.

B. Topoisomerase poison: non-Intercalating

The following structures are classed as poisons
rather than inhibitors because they stabilize the normally
transient cleavable complex that is formed between DNA
and topoisomerase enzymes, thus inhibiting the rejoining of
the DNA strand or strands.
The anticancer agent’s Etoposide and Teniposide belong
to a group of compounds called the podophyllotoxins, and are semi-
synthetic derivatives of epipodophyllotoxin —an isomer of a
naturally occurring agent called podophyllotoxin. Both agents act as
topoisomerase poisons.

Camptothecin is a natural product that was extracted from a Chinese bush

(Camptotheca acuminata) in 1966. It stabilizes the cleavable complex formed
between DNA and the enzyme topoisomerase I.

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The antibacterial quinolones and fluoroquinolones are

synthetic agents that inhibit the replication and transcription of
bacterial DNA by stabilizing the complex formed between DNA
and bacterial topoisomerases. Inhibition arises by the formation
of a ternary complex involving the drug, the enzyme, and bound
DNA.

C. Alkylating and Metalating Agents

Alkylating agents are highly electrophilic compounds that react with nucleophiles to form strong covalent
bonds. There are several nucleophilic groups present on the nucleic acid bases of DNA which can react with
electrophiles—in particular the N- 7 of guanine.

Miscoding due to alkylated guanine units is also possible. The guanine base usually exists as the keto
tautomer, allowing it to base-pair with cytosine. Once alkylated, however, guanine prefers the enol tautomer and is
more likely to base pair with thymine. Such miscoding leads ultimately to an alteration in the amino acid sequence
of proteins, which, in turn, can lead to disruption of protein structure and function.

1. Nitrogen Mustards
The nitrogen mustards get their name because they are related to the Sulphur-containing mustard gases
used during World War I. In 1942, the nitrogen mustard compound chlormethine was the first alkylating agent
to be used medicinally, although full details were not revealed until after the war owing to the secrecy
surrounding all nitrogen mustards. The nitrogen atom is able to displace a chloride ion intramolecularly to form
the highly electrophilic aziridinium ion.

2. Nitrosoureas
The anticancer agents
lomustine and carmustine
were discovered in the
1960s, and are
chloroethylnitrosoureas
which decompose
spontaneously in the body
to form two active compounds—an alkylating
agent and a carbamoylating agent. The
organic isocyanate that is formed
carbamoylates lysine residues in proteins and
may inactivate DNA repair enzymes.
Streptozotocin is a naturally occurring
nitrosourea isolated from Streptomyces
achromogenes.

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3. Busulfan
Busulfan was synthesized in
1950 as part of a systematic
search for novel alkylating agents.
It is an anticancer agent which
causes interstrand cross-linking
between guanine units. The
sulphonate groups are good
leaving groups and play a similar
role to the chlorines in the nitrogen
mustards. However, the mechanism involves a direct S N2 nucleophilic substitution of the sulphonate groups
and does not involve any intermediates such as the aziridinium ion.

4. Cisplatin
Cisplatin is one of the most frequently used anticancer drugs in medicine. Its discovery was fortuitous in
the extreme, arising from research carried out in the 1960s to investigate the effects of an electric current on
bacterial growth.

5. Dacarbazine and Procarbazine

Dacarbazine and procarbazine are
prodrugs which generate a methyldiazonium ion
as the alkylating agent. The antitumor properties
of procarbazine were discovered in the 1960s
following the screening of several hundred
compounds that had been prepared as potential
antidepressants. Temozolomide also acts as a
prodrug and is hydrolyzed in the body to form
MTIC (5-(3-methyltriazen-1-yl) imidazole-4-carboxamide), which decomposes in a similar fashion to form the
methyldiazonium ion. The O6 oxygen atom of guanine groups are particularly methylated by this agent.

6. Mitomycin C
Mitomycin-C was discovered in the 1950s and is a naturally occurring compound obtained from the
microorganism Streptomyces caespitosus. It is one of the most toxic anticancer drugs in clinical use and acts
as a prodrug, being converted to an alkylating agent within the body.

D. Chain Cutters
‘Chain cutters’ cut the strands of DNA and prevent the enzyme DNA ligase from repairing the damage.
They appear to act by creating radicals on the DNA structure. These radicals react with oxygen to form peroxy
species and the DNA chain fragments. The bleomycin and the podophyllotoxins are examples of drugs that
can act in this way, as are the nitroimidazoles and nitrofurantoin, which target bacterial DNA and are used as
antibacterial agents.
Another example is the antitumor agent calicheamicin γ1, which was isolated from a bacterium. This compound
binds to the minor groove of DNA and cuts the DNA chain.

E. Chain Terminators
Chain terminators are drugs that act as ‘false substrates’ and are incorporated into the growing DNA
chain during replication. Once they have been added, the chain can no longer be extended and chain growth is
terminated. The drugs which act in this way are ‘mistaken’ for the nucleotide triphosphates that are the authentic
building blocks for DNA synthesis.
Chain terminators, therefore, have to satisfy three conditions.

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• Firstly, they have to be recognized by the DNA

template by interacting with a nucleic acid base
on the template strand.
• Secondly, they should have a triphosphate
group such they can undergo the same enzyme
catalyzed reaction mechanism as the normal
building blocks.
• Thirdly, their structure must make it impossible
for any further building blocks to be added.
Acyclovir is an important antiviral drug that was
discovered in the 1970s, and acts as a chain terminator, satisfying all three requirements.

F. Agents that Act on RNA

1. Agents that bind to Ribosome (50s & 30s)
A large number of clinically important antibacterial agents prevent protein synthesis in bacterial cells by
binding to ribosomes and inhibiting the translation process.
2. Antisense Therapy
A great deal of research has been carried out into the possibility of using oligonucleotides to block the
coded messages carried by mRNA.
There are several advantages to this approach.
• First of all, it can be highly specific. Statistically, an oligonucleotide of 17 nucleotides should be specific for a
single mRNA molecule and block the synthesis of a single protein.
• Secondly, because one mRNA leads to several copies of the same protein, inhibiting mRNA should be more
efficient than inhibiting the resulting protein. Both these factors should allow the antisense drug to be used in
low doses and result in fewer side effects than conventional protein inhibition.
MISCELLANEOUS DRUG TARGETS

A. Transport Protein as Drug Targets

Transport protein have a binding site which ‘recognizes’ and binds a specific guest molecule, but it is
sometimes possible to fool a transport protein into accepting a drug that resembles the usual guest. If that drug
remains strongly bound to the transport protein, it will prevent the protein from carrying
out its normal role. Some important drugs operate in this way.
example is the anti-obesity drug sibutramine, which acts centrally to inhibit
the reuptake of serotonin, noradrenaline, and, to a lesser extent, dopamine. It is
thought that the increase in serotonin levels dulls the appetite. Sibutramine was
introduced in 1997 and is chemically related to the amphetamines. However, it was
withdrawn in 2010 as a result of side effects.

B. Structural Proteins as Drug Targets

1. Viral Structural Protein as drug targets
Viruses consist of a nucleic acid encapsulated within a protein coat called a capsid. If a virus is to multiply within
a host cell, this protein coat has to be dismantled in order to release the nucleic acid into the cell. Drugs have
been designed which bind to the structural proteins that make up the capsid and which prevent the uncoating
process. The drugs concerned show potential as antiviral agents against the cold virus.

2. Tubulin as drug target

The role of the structural protein tubulin in cell division—a process which involves the polymerization and
depolymerization of microtubules using tubulin proteins as building blocks. A variety of drugs interfere with
this process by either binding to tubulin and inhibiting the polymerization process, or binding to the
microtubules to stabilize them and thus inhibit depolymerization.

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a. Agents that inhibit tubulin polymerization

Colchicine is an example of a drug that binds to tubulin and
prevents its polymerization. It can be used in the treatment of gout by
reducing the mobility of neutrophils into joints.

Vinca alkaloids vincristine, vinblastine,

vindesine, and vinorelbine bind to
tubulin to prevent polymerization and are
useful anticancer agents. A range of
other natural products have also been
found to prevent the polymerization of
microtubules and are currently being
studied as potential anticancer agents.

b. Agents that inhibit tubulin

depolymerization
Paclitaxel (Taxol) and the semi-
synthetic analogue docetaxel are
important anticancer agents that inhibit
tubulin depolymerization. Paclitaxel itself
was isolated from the bark of yew trees
(Taxus spp.) and identified in 1971 following
a screening program for new anticancer
agents carried out by the US National
Cancer Institute.

C. Biosynthetic Building Block as Drug Targets

The target for the antibacterial agent Vancomycin is rather unique in that it is a biosynthetic building
block. Essentially, vancomycin ‘caps’ the building block and prevents its incorporation into the growing bacterial
cell wall. There is a small peptide chain on the building block which can bind to vancomycin by hydrogen bond
interactions. Indeed, vancomycin acts like a receptor by providing a binding site for the building block.

D. Biosynthetic Processes as Drug Targets: Chain Terminators

Puromycin is an antibiotic which can be viewed in
the same light, except that it terminates the growth of protein
chains during translation. It is able to carry out this role
because it mimics the terminus of an aminoacyl-tRNA
molecule. Aminoacyl-tRNA is the molecule that brings an
amino acid to the ribosome such that it can be added to the
growing protein chain.

E. Protein-Protein Interactions
One way of inhibiting protein–protein interactions is
to use antibodies. These agents have been particularly
successful in preventing protein–protein interactions for a family of extracellular proteins called integrins.
Indeed, daclizumab is an antibody used as an immunosuppressant in kidney transplants, while
abciximab is an antibody fragment that inhibits blood clotting following angioplasty procedures aimed at
unblocking coronary arteries.

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Tirofiban, which is used as an anticoagulant by preventing

protein–protein binding between an integrin and the blood-clotting
agent fibrinogen. It is thought that the drug mimics a tripeptide
sequence (Arg–Gly–Asp) in fibrinogen that plays an important role in
the binding process between the two proteins.

F. Lipids as Drug Targets

The number of drugs that interact with lipids is relatively small and, in general, they all act in the same way—
by disrupting the lipid structure of cell membranes. It has been proposed that general anesthetics work by
interacting with the lipids of cell membranes to alter the structure and conducting properties of the membranes.
Another agent thought to disrupt cell membrane structure is the anticancer agent Cephalostatin 1, which is
thought to span the phospholipid bilayer. Finally, daptomycin is an antibiotic that disrupts multiple functions of
the bacterial cell membrane.

1. Tunnelling Molecules
The antifungal agent amphotericin B (used
topically against athlete’s foot and systemically
against life-threatening fungal diseases) interacts
with the lipids and sterols of fungal cell membranes
to build ‘tunnels’ through the membrane.
The tunnel resulting from this cluster is lined with the
hydroxyl groups and so it is hydrophilic, allowing the
polar contents of the cell to drain away. The
compound is a natural product derived from a
microorganism (Streptomyces nodosus). Recently,
it has been established that each molecule of amphotericin
forms a hydrogen bonding interaction with a molecule of
ergosterol in order to create the ion pore channel.

The antibiotic gramicidin A is a peptide containing 15 amino

acids which is thought to coil into a helix such that the outside
of the helix is hydrophobic and interacts with the membrane
lipids, while the inside of the helix contains hydrophilic
groups, thus allowing the passage of ions.

2. Ion Carriers
Valinomycin is a cyclic structure obtained from Streptomyces
fermentation. It contains three molecules of l-valine, three molecules
of d-valine, three molecules of l-lactic acid, and three molecules of d-
hydroxyisovalerate. Th ese four components are linked in an ordered
fashion such that there is an alternating sequence of ester and amide
linking bonds around the cyclic structure. This is achieved by the
presence of a lactic or hydroxyisovaleric acid unit between each of
the six valine units.

G. Carbohydrates as Drug Targets

1. Glycomics
The term glycomics is used to describe the study of carbohydrates,
either as drugs or as drug targets. Carbohydrates are polyhydroxy structures, many of which have the general
formula CnH2nOn. Examples of some simple carbohydrate structures include glucose, fructose, and ribose.
2. Antigens and Antibodies

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The molecular tags that act as cell recognition molecules commonly act as antigens if that cell is introduced
into a different individual. When we suffer a bacterial infection, the immune system recognizes foreign
molecular tags and produces antibodies which bind to them and trigger an immune response aimed at
destroying the invader.
3. Cyclodextrins
Cyclodextrins are macrocyclic structures made up of carbohydrate building blocks. As the interior of
cyclodextrins is relatively hydrophobic and can accommodate drug-sized molecules, cyclodextrins have been
extensively studied as a means of drug delivery for hydrophobic drugs. Moreover, a novel application has
recently been approved for a cyclodextrin called Sugammadex, which acts as a ‘scavenger’ for the
neuromuscular agent rocuronium.
CHECK FOR UNDERSTANDING (25 minutes)

You will answer and rationalize this by yourself. This will be recorded as your quiz. One (1) point will be given to correct
answer and another one (1) point for the correct ratio. Superimpositions or erasures in you answer/ratio is not allowed. You
are given 25 minutes for this activity:

Multiple Choice

1. A reversible inhibitor is one that, once removed, allows the enzyme it was inhibiting to begin working again.
It will bind to the enzyme using a covalent bond at the active site which therefore makes the enzyme denatured.
a. First Statement is true, second statement is false
b. First statement is False, second statement is true
c. Both are true
d. Both are false
ANSWER: ________
RATIO:___________________________________________________________________________________________
_________________________________________________________________________________________________

2. Renin inhibitors block the enzyme renin from triggering a process that helps regulate blood pressure by inhibiting
the activity of renin that is responsible for hydrolyzing _________?
a. Angiotensin to Angiotensin I
b. Angiotensin I to Angiotensin II
c. Angiotensinogen to Angiotensin I
d. Angiotensinogen to Angiotensin II
ANSWER: ________
RATIO:___________________________________________________________________________________________
_________________________________________________________________________________________________

3. Previously called actinomycin D; is a naturally occurring antibiotic that was first isolated from Streptomyces parvullis in
1953.
a. Doxorubicin
b. Daptomycin
c. Dactinomycin
d. Dentomycin
ANSWER: ________
RATIO:___________________________________________________________________________________________
_________________________________________________________________________________________________

4. Prevent the action of an agonist without any effect on the binding of the agonist to the receptor.
a. Irreversible antagonist
b. Non-competitive antagonist
c. Silent antagonist

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d. Insurmountable antagonist
ANSWER: ________
RATIO:___________________________________________________________________________________________
_________________________________________________________________________________________________

5. Covalent Bond The first alkylating agent to be used medicinally.

a. Nitrogen Mustards
b. Nitrosoureas
c. Busulfan
d. Cisplatin
ANSWER: ________
RATIO:___________________________________________________________________________________________
_________________________________________________________________________________________________

6. A drug that binds to tubulin and prevents its polymerization and used in gout by reducing the mobility of neutrophils into
joints.
a. Febuxostat
b. Colchicine
c. Allopurinol
d. Indomethacini
ANSWER: ________
RATIO:___________________________________________________________________________________________
_________________________________________________________________________________________________

7. A type of adrenergic receptor which is located at the bronchioles of the lungs and has a stimulating effect on smooth
muscles.
a. Alpha1
b. Alpha2
c. Beta1
d. Beta2
ANSWER: ________
RATIO:___________________________________________________________________________________________
_________________________________________________________________________________________________

8. I. Topoisomerase poisons are believed to bind to DNA, the topoisomerase, or either molecule at or near the region
of the enzyme involved in the formation of the DNA-protein covalent linkage.
II. Intercalating agents are capable of inserting themselves between the successive bases in DNA, thus kinking,
uncoiling or otherwise deforming it and therefore preventing its proper functioning.
a. First Statement is true, second statement is false
b. First Statement is false, second statement is true
c. Both are true
d. Both are false
ANSWER: ________
RATIO:___________________________________________________________________________________________
_________________________________________________________________________________________________

9. This antifungal drug believed to interact with membrane sterols (ergosterol in fungi) to produce an aggregate that
forms a transmembrane channel or a bore.
a. Amphotericin A
b. Amphotericin B
c. Itraconazole
d. Gramicidin A

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ANSWER: ________
RATIO:___________________________________________________________________________________________
_________________________________________________________________________________________________

10. Occurrence when an agonist is bound to its receptor for a long period of time
a. Exposure
b. Allergy
c. Sensitization
d. Desensitization
ANSWER: ________
RATIO:___________________________________________________________________________________________
_________________________________________________________________________________________________

RATIONALIZATION ACTIVITY (THIS WILL BE DONE DURING THE FACE TO FACE INTERACTION)
The instructor will now rationalize the answers to the students. You can now ask questions and debate among
yourselves. Write the correct answer and correct/additional ratio in the space provided.

1. ANSWER: ________
RATIO:_______________________________________________________________________________________
_____________________________________________________________________________________________
_____________________________________________________________________
2. ANSWER: ________
RATIO:_______________________________________________________________________________________
_____________________________________________________________________________________________
_____________________________________________________________________
3. ANSWER: ________
RATIO:_______________________________________________________________________________________
_____________________________________________________________________________________________
_____________________________________________________________________
4. ANSWER: ________
RATIO:_______________________________________________________________________________________
_____________________________________________________________________________________________
_____________________________________________________________________
5. ANSWER: ________
RATIO:_______________________________________________________________________________________
_____________________________________________________________________________________________
_____________________________________________________________________
6. ANSWER: ________
RATIO:_______________________________________________________________________________________
_____________________________________________________________________________________________
_____________________________________________________________________
7. ANSWER: ________
RATIO:_______________________________________________________________________________________
_____________________________________________________________________________________________
_____________________________________________________________________
8. ANSWER: ________
RATIO:_______________________________________________________________________________________
_____________________________________________________________________________________________
_____________________________________________________________________
9. ANSWER: ________
RATIO:_______________________________________________________________________________________
_____________________________________________________________________________________________

This document is the property of PHINMA EDUCATION

 PHA 051: Pharmaceutical and Medicinal Chemistry
Module #3 Student Activity Sheet

_____________________________________________________________________
10. ANSWER: ________
RATIO:_______________________________________________________________________________________
_____________________________________________________________________________________________
_____________________________________________________________________

LESSON WRAP-UP (10 minutes)

You will now mark (encircle) the session you have finished today in the tracker below. This is simply a visual to help you
track how much work you have accomplished and how much work there is left to do.

You are done with the session! Let’s track your progress.

PERIOD 1 PERIOD 2 PERIOD 3

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

AL Strategy: CAT: 3-2-1

Three things you learned:
1) ______________________________________________________________________________________________
2) ______________________________________________________________________________________________
3) ______________________________________________________________________________________________

Two things that you’d like to learn more about:

1) ______________________________________________________________________________________________
2) ______________________________________________________________________________________________

One question you still have:

1) ______________________________________________________________________________________________

This document is the property of PHINMA EDUCATION