CHEM 453

PHYSIOLOGICALLY ACTIVE
COMPOUNDS

By: Prof. Akwasi Acheampong

TA: Benjamin Gyedu Akonor

 Course Outline
1. Physiologically active compounds:
- Drugs and their sources
- Drugs nomenclature
- Orthodox and traditional medicine
- Phytochemical screening
2. Chemotherapeutic Agents
- Classes
- X’tics and activities of antibiotics and anti-malarials
 Course Outline
3. Pharmacodynamic Agents

4. Vitamins

5. Hormones

6. Pheromones

7. Other Biologically active substances. Eg. pesticides

 Introductory concepts:
MEDICINAL CHEMISTRY
• It is a field of science which overlaps the
disciplines of chemistry, biochemistry, cell
biology and pharmacology.

• Modern medicine (excluding surgery, diet,

exercise etc) relies heavily on drugs as the
main tool of therapeutics (healing effects)
 MEDICINAL CHEMISTRY
• Scientific medical model or therapeutics,
attributes disease to an underlying
derangement of normal function that can be
defined in biochemical or structural terms
detected by objective means and influenced
beneficially by appropriate chemical or
physical interventions.
 MEDICINAL CHEMISTRY
• ‘Alternative’ or ‘Holistic’ or ‘Complementary’
medical systems have bases which lie outside
the domain of science.
• They include
1. Allopathy
2. Homeopathy
3. Faith Healings etc.
 MEDICINAL CHEMISTRY

• Drugs are compounds which interact with a

biological system to produce a biological
response
• Life is made up of cells, hence drugs must act
on cells.
• Different drugs act at different locations in the
cell.
• There are four main molecular targets: Lipids,
carbohydrates, proteins and nucleic acids.
 WHAT IS A DRUG
• General: A substance which may have medicinal,
intoxicating, performance enhancing or other
effects when taken or put into a human body or the
body of another animal and is not considered a
food or exclusively a food.

• In pharmacology: It is ‘a chemical substance used in

the treatment, cure, prevention, or diagnosis of
disease or used to otherwise enhance physical or
mental well-being’.
 WHAT IS A DRUG
• The American Heritage Dictionary: two definitions:
a) It is a chemical substance, especially one
prescribed by a medical provider, that is used in the
diagnosis, treatment, or prevention of a condition or
diseased.

b) It is a chemical substance such as a narcotic or a

hallucinogen that affects the central nervous system
and is used recreationally for perceived desirable
effects on personality, perception, or behaviour.
 WHAT IS A DRUG
• It is any chemical you take that affects the way
your body works.

• It is any substance which can alter the

structure or function of the living organism.

• N/B: All medicines are drugs but not all drugs

are medicines.
 Examples of Drugs
• Coffee, tea,
• Tobacco, alcohol
• Pollutants , pesticides
• Vitamins etc.
• Analgesics
• Anti-malarials etc
 DRUGS AND FOOD
• What is considered a drug rather than a food
varies between cultures.
• The distinction is enshrined in laws which vary
between jurisdictions and aim to restrict or
prevent drug use.
• The status of a substance may be uncertain or
contested with respect to whether it is a drug.
• There are different meanings in drug control
law, govt regulations, medicine, and colloquial
usage.
 DRUGS AND FOOD
• Many natural substances, such as beers,
wines, and psychoactive mushrooms, blur the
line between food and recreational drugs
since they affect the functioning of both mind
and body when ingested.
 DRUG DISCOVERY
• Medicines consisted of herbs and potions before
the 20th century.

• Efforts to isolate and purify the active principles

in these medicines led to the birth of
pharmaceutical companies.

• Chemists synthesized the analogues of these

active principles (lead compounds) in an attempt
to improve on what nature had provided.
 DRUG DISCOVERY
• Major stages in drug discovery and
development include:
i. Choosing a disease
ii. Choosing a drug target
iii. Identify bioassay
iv. Find a lead compound
v. Isolate and purify lead compound if
necessary
vi. Determine the structure of the lead
compound
 DRUG DISCOVERY
vii. Identify structure-activity relationship (SAR)
viii. Identify the pharmacophore (next 2 slides)
ix. Improve target interactions
x. Improve pharmacokinetic properties
xi. Patent the drug
xii. Study drug metabolism
xiii. Test for toxicity
xiv. Design a manufacturing process
 DRUG DISCOVERY
• Carry out clinical trials
• Make the drugs
• Make money

• N/B: Many of the stages run concurrently and

are dependent on each other.
 A PHARMACOPHORE
• A pharmacophore is an abstract description of
molecular features which are necessary for
molecular recognition of a ligand by a
biological macromolecule.
• The IUPAC defines a pharmacophore to be "an
ensemble of steric and electronic features that
is necessary to ensure the optimal
supramolecular interactions with a specific
biological target and to trigger (or block) its
biological response".
 A PHARMACOPHORE
• A pharmacophore model explains how
structurally diverse ligands can bind to a
common receptor site.
• Furthermore pharmacophore models can be
used to identify through denovo design or
virtual screening novel ligands that will bind to
the same receptor.
 CLASSIFICATION OF NATURAL (PLANT)
DRUGS.
• In Pharmacognosy, drugs may be classified
according to:
- Their morphology: Here, drugs are grouped
according to the part of the plant or animal
represented, such as roots, leaves, organs or
glands.
- The taxonomy of the plants and animals from
which they are obtained: Large numbers of plant
families have certain distinguishing characteristics
that permit drugs from these families to be
studied.
 CLASSIFICATION OF NATURAL (PLANT)
DRUGS.

- Their therapeutic or pharmacologic

applications. E.g. antimalarial, antiviral etc.

- Their chemical constituents: this appears to

be the preferred method of classification since
the activity and therapeutic use of drugs are
based on chemical constituents. E.g.
Sulphonamides, Phenolics etc
 CLASSIFICATION OF SYNTHETIC DRUGS.
• They are grouped according to many criteria
which include:
a. Therapeutic or Pharmacological perspective.
This classifies drugs according to the
biological effect they possess. Eg; Analgesics,
antipsychotics, antihypertensive, anti-
asthmatics, antibiotics etc.

- Useful when one wishes to know the full

scope of drugs available for a certain ailment.
CLASSIFICATION OF SYNTHETIC DRUGS
• b) Organic chemical or chemical structure
Approach:
- Drugs with a common skeleton are grouped
together. E.g. Penicillins, barbiturates,
opiates, steroids etc.
E.g. penicillins: the antibiotic activity of
penicillins are the same.
Barbiturates have common skeleton but
have completely different uses in medicine.
Steroids have common skeleton but have
completely different uses in medicine.
CLASSIFICATION OF SYNTHETIC DRUGS
• c) Target System Approach:
Here drugs are classified according to
whether they affect a certain target system in
the body (usually involving a chemical
messenger).
Eg; antihistamines, cholinergics etc.
CLASSIFICATION OF SYNTHETIC DRUGS
d) Site of action approach:
Here, drugs are grouped according to the
enzyme or receptor with which they interact.
Eg; anticholinesterase – a group of drugs
which act through inhibition of the enzyme
acetyl cholinesterase
• This approach is Biochemical mechanistic.
 CLASSIFICATION OF SYNTHETIC DRUGS
Drugs can be divided into 5 main groups based
on the widely accepted pharmacological
approach. They are:
• Pharmacodynamic agents
• Chemotherapeutic agents
• Nutritional products – vitamins
• Hormones
• Miscellaneous agents
 COMPONENTS OF A DRUG
• Composed of two main parts
- Active ingredient
- Inactive ingredient (excipients)
• Active ingredient is responsible for the action
of the drug.
• Inactive ingredient only helps to formulate the
drug into a required form, i.e syrup, tablet,
capsule etc. Eg; sugar, water, flavour,
preservative etc.
 NOMENCLATURE OF DRUGS
• At least three names are known for drugs:
- Code No. or Code Designation
- Chemical name
- Proprietary, Trivial, Brand, Tradename or
Trademark.

• Code No. or Code Designation: Usually formed with the initials

of the laboratory or the chemist or the research group/team
that prepared or tested the drug the first time, followed by a
number.
E.g. ICI (Imperial Chemical Industry; antimarials in 1950s).
M&B 760 (Meyer and Baker; for thiazamide in the early 1960s)

• It is later replaced by a chosen adequate name.

 DRUG ACTION
• To keep body healthy and functioning, a
significant array of chemical reactions take place
within the body.
• Life is made up of cells, hence drugs act on cells.
• Cells are made up of four fundamental molecular
building blocks
i. Lipids
ii. Carbohydrates
iii. Proteins
iv. Nucleic acids
FACTORS AFFECTING BIOACTIVITY
• The biochemical system encountered by a
drug molecule are extremely complex.

• Factors affecting a drugs interactions with and

contributing to its final effects are very many.

• There are three (3) major categories of factors

 FACTORS AFFECTING BIOACTIVITY
• The factors are:
1. Physicochemical properties
i. Solubility
ii. Partition coefficient
iii. Ionization

2. Chemical Structure parameters

iv. Resonance
v. Inductive effect
vi. Oxidation potentials
vii. Types of bonding
viii. Isosterism
FACTORS AFFECTING BIOACTIVITY
3. Spatial considerations

i. Molecular dimensions

ii. Interatomic distances

iii. Stereochemistry
 MECHANISM OF DRUG ACTION
• At the molecular level (medicinal chemist), the
mechanism of action of drugs can be put in
the following classes:
a) Drugs acting on enzymes
b) Drugs which act by suppressing gene function
c) Drugs acting as anti-metabolites
d) Drugs acting as chelating agents
e) Drugs acting on biological membranes
f) Non-specific action of drugs
 MECHANISM OF DRUG ACTION
• It is impossible to produce a general mechanism
of action for drugs because:
a) There are structural diversities of drug
molecules.
b) There is an ever increasing new knowledge on
the mechanisms of action of drugs.
c) There are drugs whose mechanisms of action
are not known.
d) There are drugs whose mechanism of action
can be classified into two or more classes.
ORTHODOX AND TRADITIONAL MEDICINE
• ORTHODOX medicine refers to
- the conventional form of medicine or
- currently accepted form of medicine or
- scientific form of medicine or
- modern form of medicine

• TRADITIONAL medicine refers to

- Folkloric medicine
- Herbal / plant medicine
- Native medicine
ORTHODOX AND TRADITIONAL MEDICINE
DISCUSSIONS in class:
• Advantages and disadvantages of Orthodox
medicine
• Advantages and disadvantages of Traditional
medicine
• Advantages of Orthodox over traditional
• Advantages of traditional over orthodox

Assignment: make detailed notes on the above

subjects.
 PHYTOCHEMICAL SCREENING
• This is a process of tracing plant constituents.
• It involves an array of simple tests to test for the
presence of physiologically active compounds.
• It involves the use of different chemicals and reagents
that enable us find if a plant material contains:
i. Alkaloids vi. Flavonoids
ii. Tannins vii. Saponins
iii. Steroids/Terpenoids viii. Antraquinones
iv. Carotenoids ix. Coumarins etc.
v. Phenolics

Ques. Describe the test for analysing cpds iv, vi, viii and ix.
 Phytochemical screening
Constituent TEST OBSERVATION
Alkaloids About 0.2g of the extracts is warmed Orange red precipitate
with 2% H2SO4 for two minutes. It is indicate the presence of
then filtered and a few drops of alkaloids.
Dragondorff reagent added.

Tannins A small quantity of each extracts is A dark green solution

mixed with water and heated on indicates the presence of
water bath and filtered. A few drops tannins
of ferric chloride is added to the
filtrate.
Anthraquinones About 0.5 g of the extract is boiled Formation of rose-pink
with 10 % HCl for few minutes in color indicates the presence
water bath. It is then filtered and of anthraquinones.
allowed to cool. Equal volume of
CHCl3 is added to the filtrate. Few
drops of 10% ammonia is then added
to the mixture and heated.
 Phytochemical screening

Constituent TEST OBSERVATION

Tannins A small quantity of each extracts is mixed A dark green solution

with water and heated on water bath and indicates the presence of
filtered. A few drops of ferric chloride is tannins.
added to the filtrate.

Steroids 2 ml of acetic anhydride is added to 0.5 g The colour changed from

of the extract of each with 2 ml of H2S04 . violet to blue or green in
some samples indicate
presence of steroids.

Terpenoids 0.2 g of the each extract is mixed with 2 A reddish brown coloration
(Salkowski ml of chloroform (CHCl3 ) and of the interface formed
Test): concentrated H2SO4 (3ml) is carefully indicates positive results
added to form a layer. for the presence of
terpenoids.
 CHEMOTHERAPEUTIC AGENTS
• These are compounds of definite structure used
in the treatment and cure of infectious
diseases.
• They are classified according to the parasites on
which they act.
i. Antimalarial vi. Antiviral
ii. Antifungal v. Antiseptic and Disinfectant
iii. Antiprotozoal
iv. Antihelmintic
v. Antineoplastic
 CHEMOTHERAPEUTIC AGENTS
• The IDEAL chemotherapeutic agent
- must be selectively toxic to the parasite
- must be innocuous or harmless to the host
(human).

• Chemotherapeutic agents makes use of the

morphological and biochemical differences
between the invading cell or parasite and the
host.
 CHEMOTHERAPEUTIC AGENTS
• Chemotherapeutic index: It is
- the relative efficiency and safety of
chemotherapeutic agents
- expressed by the relationship ratio of maximum
tolerated dose by the host to the minimum curative
dose.

• The greater the index, the better is the

chemotherapeutic agent.
- agent is more safe for the patient and large doses
may be safe for humans but very small doses affect
the parasite.
 RESISTANCE TO CHEMOTHERAPEUTIC AGENTS

• The promiscuous and improper use of many

chemotherapeutic agents has contributed to
the emergence of resistant strains of micro-
organisms or parasites to them.

• The most serious clinical consequence is that

the bacteria will require a massive dose,
usually more than the host can tolerate before
they are injured.
ACQUISITION OF RESISTANCE BY MICRO-ORGANISMS

Micro-organisms are known to acquire

resistance by:
• Exclusion of the drug from the target, either
by decreased cell wall permeability or
destruction of the drug
• Formation of adaptive drug inactivating
enzymes
• Decrease of the agent-modifying enzymes
• Increased concentration of metabolite
antagonizing the drug action
ACQUISITION OF RESISTANCE BY MICRO-ORGANISMS

• Mutation by gene transfer

• Cross resistance
 OVERCOMING DRUG RESISTANCE
The development of resistance strains may be
avoided by :

• Properly adjusting the dose and period of

administration.

• Utilizing a combination of several drugs e.g.

amodiaquine-artesunate for malaria
treatment
 INTRODUCTORY MICROBIOLOGY
• MICROBE: generally used to describe bacteria,
fungi and viruses.
• PARASITE: generally used to describe protozoa
and helminthes (worms)
• DIVERSITY : refers to the many different types
of organisms on earth.
• CLASSIFICATION: living organisms classified
according to how recently one type of
organism shared a common ancestor with
another type of organism.
 INTRODUCTORY MICROBIOLOGY
• Living organisms are classified as either:
- Prokaryotes ; consisting of cells without
nucleus (eg. bacteria).

- Eukaryotes; consisting of cells with nucleus

(eg. Protozoa, fungi, helminthes).
• An organism is assigned to specific:
- Domain Kingdom Division or
- Phylum Class Order Family Genus
Species
 NOMENCLATURE OF MICROBES
• The genus name is normally a description of
the shape and arrangement of the micro-
organism.
Examples:
BACILLUS - rod shaped
STREPTOCOCCUS – chain of berries
STAPHYLOCOCCUS - Bunch of berries
CLOSTRIDIUM - spindle shaped
SPIRILLUM - spiral shaped
 NOMENCLATURE OF MICROBES
• The Genus name could also be named after
the microbiologist who first described the
bacterium.
E.g. PASTEURELLA (after Louis Pasteur)

SALMONELLA (after Salmon, American microbiol.)

ESCHERICHIA (after Theodor Escherichia, German )

 NOMENCLATURE OF MICROBES
• The genus can also be named in honour of
somebody else.
E.g. LEGIONELLA (after the American
Legionaries who died in the first recognized
outbreak of the disease it caused).

• SPECIES name may often refer to the disease

the bacterium causes:
Salmonella typhii causes typhoid
Streptococcus pneumonia causes pneumonia
 NOMENCLATURE OF MICROBES
• The SPECIES name may also recognize a
specific characteristic of the organism:

staphylococcus aureus (produces a golden

pigment on certain media)

streptococcus equi (infects horses only)

micrococcus roseus (produces a reddish

pigment)
 INFECTIOUS DISEASES
• Bacterial diseases endemic in West Africa:
i. Leprosy
ii. Tuberculosis
iii. Bacillary dysentery
iv. Enteric fevers
v. Undulant fevers

• Fungal disease:
i. Ring worm
ii. Pityrioasis
iii. aspergilosis
 INFECTIOUS DISEASES
• Viral Diseases:
i. Yellow fever
ii. Rabies
iii. Poliomyelitis
iv. Trachoma
v. Influenza
vi. Measles

• Protozoa Diseases:
i. Malaria
ii. Amoebic dysentery
 INFECTIOUS DISEASES
• Metazoal Diseases:
i. Hookworm
ii. Whipworm
iii. Pinworm
iv. Roundworm
v. Guinea worm
vi. Blinding worm (onchocerciasis)
vii. Flukes (Bilhazia)
 ANTIBIOTICS
• ANTIBIOTICS: They are anti-infective agents
derived from natural sources.

• ANTIMICROBIALS: They are anti-infective

agents produced from synthetic substances.

• N/B: Terms are used interchangeably

 CLASSIFICATION OF ANTIBIOTICS
• BIOGENIC BASES : Includes
a) Those derived from Amino acids
eg. Penicillin, Cephalosporins,
Chloramphenicol , Cycloserine etc
b) Those derived from polypeptides
eg Viomycin, Polymycin B, Bacitracin etc.
c) Those derived from sugars
eg. Streptomycn, Kanamycin, Neomycin,
Paromycin
d) Those derived from acetate or proprionate units
eg. Tetramyclines, Erythromycin, Griseofulvin
 CLASSIFICATION OF ANTIBIOTICS
• ACCORDING TO MECHANISM OF ACTION:
a) Those which inhibit synthesis of bacterial
cell walls or activate the enzymes that disrupt
bacterial cell walls.
eg. Penicillin, Vancomycin, Cephalosporins

b) Those which cause increased permeability of

bacterial cell membrane with leakage of
essential intracellular components.
eg. Polymycin, Amphotericin B, Polyenes etc
 CLASSIFICATION OF ANTIBIOTICS
c) Those which inhibit bacterial protein synthesis by
inhibition of ribosomal function.
eg. Chloramphenicol, tetracyclines (C22H24N2O8 )

d) Those which interfere with the transcription of

mRNA.
eg. Gentamycin, Kanamycin,
Streptomycin (C21H39N7O12),3H2SO4 = 1457

e) Those which interfere with bacterial nucleic acid

synthesis.
eg. Rifampicin, Anthracyclines
 CLASSIFICATION OF ANTIBIOTICS
• ACCORDING TO CHEMICAL STRUCTURE:
a) -Lactam antibiotics
eg. Penicillins, Cephalosporins, Clavulanic
acid, monobactams etc.
b) Non-Lactam antibiotics
eg. Tetracyclines, amino glycosides,
polypeptides, polyenes, macrolides
c) Unclassified
eg. Chloramphenicol, Novobiocin, Fusidic acid
 -Lactam antibiotics
• They contain the -Lactam ring
RCO
Penicillin S
HN CH3

CH3

N
O
COOH

RCO
S

Cephalosporins HN

N CH2R2
O

COOH
Cephalosporin
 PENICILLINS
• They are characterized by three fundamental
structural requirements:
a) Fused B-Lactam ring
b) Free carboxyl group
c) One or more properly substituted amino side
chain groups.

• The basic structure consists of

i) Thiazolidine ring fused with
ii) -Lactam ring to which is attached
iii) An amide side chain
 PENICILLINS

RCO
Amide
Side chain S
HN CH3

CH3

N
O
COOH
 -Lactam ring Thiazolidine ring
 STR. ACTIVITY RELATIONSHIP OF PENICILLINS

The following are essential:

• The strained -Lactam ring
• The free carboxylic acid
• The bicyclic system
• The acylamino side chain
• The stereochemistry of the bicyclic ring with
respect to the acylamino side chain

N/B: The sulphur is usual but not essential

 EXAMPLES OF PENICILLINS
• Ampicillin ( C16H19N3O4S )
R= CH2

NH2

• Amoxicillin (C16H19N3O5S )
CH2
R=
NH2

HO
 NON-LACTAM ANTIBIOTICS
• Aminoglycoside Antibiotics:
-consist of aminosugars linked glycosidically
- Eg. Gentamycin, Streptomycin, Kanamycin
Neomycin etc.

• Polyenes antibiotics:
- characterized by a large ring containing a
lactone function and a sequence of conjugated
double bonds.
- can be acidic, basic, amphoteric or non-ionic
- eg. Amphotericin, Nystatin, Natamycin
 NON-LACTAM ANTIBIOTICS

• The Macrolides:
- characterized by macrocyclic ketone and
amino sugars.
- eg. Erythromycin, oleandomycin, carbomycin
 THE TETRACYCLINES
• They have the general structure

R1 R4 N(CH3)2
R2 R3
OH

CONH2
OH
O OH O
HO

• They constitute an extremely useful and effective group

of antibiotics

• They are widely used in medical practice against a large

variety of infective agents
 THE TETRACYCLINES
Official Name Brand Name R1 R2 R3 R4

Tetracycline Achromycin H CH3 OH H

Chlortetracycline Aureomycin Cl CH3 OH H

Oxytetracycline Terramycin H CH3 OH OH

Doxycycline Vibramycin H CH3 H OH

 Structural Activity Relationship (Empirical)
C. No. Structural Modification
1 Any modification
2 Acetyl group only
3 Any modification
4 Dimethylamino essential
5 OH, CH3CO-, RCO-
5a Loss of H(together with C6-OH)
6 Remove OH, CH3 or both
7 Cl,Br, NO2, (CH3)2N-
8 Little Information available
9 Cl, CH3
10, Inviolate zone
11,11a,
12
12a Epimerizing a –OH or deoxy
Effects
No antibacterial activity
Slight activity retained
No antibacterial activity
NHCH3 retains most activity
All retain activity
Inactive degradation product
Active, more stable drug
Activity retained
Decreased activity
Any change lowers or eliminates all
activity
Decreased activity
 ANTI-PROTOZOAL DRUGS
• These drugs used against diseases caused by
protozoans.

• The main protozoal diseases in Africa are

malaria, trypanosomiasis, amoebiasis etc.
 MALARIAL
• MALARIA: Caused by the infestation of
protozoan of the genus plasmodium.
• Over forty exist but only four affect man.
a) P. vivax
b) P. ovale
c) P. malariae
d) P. falciparum
 ANTI-MALA RIAL DRUGS
• These are drugs used for the treatment of malaria.
• The requirements for an ideal anti-malarial drugs:
a) Should rapidly relieve symptoms of the disease
b) Should be harmless to the patient and have no
unpleasant side effects.
c) Should preferably destroy all the stages of
development of malaria species including
gametocytes
d) Should be economically cheap and easy to
administer
CLASSES OF ANTI-MALARIAL DRUGS
1. Naturally occuring antimalarials: Eg. Quinine,
cinchonine, artemisinin.
2. 8-aminoquinolines: Eg. Primaquine,
pamaquine.
3. 4-aminoquinolines: Eg. chloroquine,
mefloquine
4. 9-aminoacridines: Eg. Mepacrine,
pyronaridine
5. Naphthoquinones: Eg. atovaquone
CLASSES OF ANTI-MALARIAL DRUGS
6. The hydrofolate reductase inhibitors:
i. Trimethoprim
ii. The biguanides; Eg. Proguanil, chlorproguanil
iii. Diaminopyrimidine derivatives;. Eg.
Pyrimethamine

7. Phenanthrene methanols: Eg. Halofantrine

(halfan)
8. Sulphonamides: Eg. Sulphadoxine
9.Other antimalarials: Eg. Desoxytetracycline
 NATURALLY OCCURING ANTIMALARIALS

ARTEMISININE (Quighaosu) and DERIVATIVES

• Artemisinine was isolated from the herb
Artemisia annua L. by Chinese scientist in
1972.
• Chemical structure:
 PROPERTIES OF ARTEMISININE
a) Soluble in organic solvent but almost insoluble in
water, making it clinically useless

b) Derivatives such as artemether, arteether (having

lipophilic moieties) and sodium Artesunate (with
lipophilic moiety) are effective and useful clinically.

c) Other derivatives such as its carboxylic esters,

carbonates and sulphonamides are more potent
than artemisinine.

d) The 1,2,4-trioxane ring structure is essential

 PROPERTIES OF ARTEMISININE
e) They present completely new chemical series
of antimalarial compounds with a high level of
blood schizontocidal activity against
chloroquine resistant strains of malarial
parasite.
 REACTIONS OF ARTEMISININE AND
DERIVATIVES
i. Artemisinine NaBH4 /MeOH Dihydroartemisinine

ii. Dihydroartemisine MeI/Ag2O Artemether

iii. Dihydroartemisine EtOH/BF3 Arteether

iv. Dihydroartemisine Succinic acid/H2SO4 Artesunate

v. Artesunate 5% NaHCO3 Sodium Artesunate

 Structural Activity Relationship
• The following general statements can be made
to summarize the structural requirements for
antimalarial activity of artemisinine
derivatives.
a) The presence of H at C-1 and C-7 is essential
for activity.
Replacement or substitution by any other
group leads to reduced or partial loss of
activity.
b) Substitution at C-2 and C-3 leads to loss of
activity
 Structural Activity Relationship
c) Presence of methyl group at C-4 increases
antimalarial activity.

d) Peroxide linkage (endoperoxide) between C-4

and C-6 is indispensable for antimalarial activity.
Hence catalytic hydrogenation of artemisinine
produces deoxyartemisinin which is devoid of
antimalarial activity.

e) Unsubstitution at C-8 and C-9 is essential for

activity. Methyl or hydroxyl group at C-9 produces
less active compounds.
 Structural Activity Relationship
• Methyl substitution at C-10 and C-11 is
essential for activity while replacement with
ethyl group produces a compound of low
activity.
• Presence of carbonyl group at C-12 may not
be essential for activity. Eg. deoxoartimisinnin
devoid of carbonyl function at C-12 is active,
while substitution at C-12 by groups such as
CH3(artemether), C2H5(arteether) lead to
increased antimalarial activity.
 Structural Activity Relationship
• Also, reduction of the carbonyl group in
artemisinin to dihydroartemisinin leads to
increased activity.
• Substitution on the lactone carbonyl markedly
increases potency.
 ANTIVIRAL AGENTS
• Viruses are small infective agents consisting
essentially of nucleic acid, RNA or DNA, enclosed
in a protein coat.
• They are not cells, having no metabolic
machinery of their own, i.e., they have to use the
metabolic processes of the host cell, which they
enter and infect.
• DNA viruses usually enter the host cell nucleus
and direct the generation of new viruses.
• RNA viruses direct the generation of new viruses,
usually without involving the host cell nucleus.
EXAMPLES OF PATHOGENIC VIRUSES
• DNA Viruses
• Pox viruses cause small pox
• Herpes viruses cause chicken pox, shingles,
and glandular fever, etc.
• Adeno viruses cause sore throat,
conjunctivitis, etc.
• Papilloma viruses cause warts.
 RNA Viruses
• Orthomyxoviruses – influenza.
• Paramyxoviruses – measles,
mumps.
• Rubella virus – German measles.
• Rhabdovirus – rabies
 RNA Viruses
• Picornaviruses – colds, meningitis,
poliomyelitis.
• Retroviruses – Acquired Immuno
Deficiency Syndrome (AIDS), T cell
leukemia
• Hepadnaviruses – Serum hepatitis
• Arboviruses – arthropod–borne
encephalitis and various fevers. Eg.
yellow fever
 ANTIVIRAL DRUGS
• Because viruses share many of the metabolic
processes of the host cell, it is difficult to find
drugs that are selective for the pathogen.
Drugs of special interest include:
• ANTI-HIV DRUGS
There are two main classes of anti-HIV drugs:
• Reverse Transcriptase Inhibitors (RTIs)
• Protease inhibitors.
 ANTI-HIV DRUGS
• Each class has a different mechanism of action
and combinations are used in the therapy of
HIV-AIDS.
• The RTIs are subdivided into Nucleoside
Reverse Transcriptase Inhibitors and non-
Nucleoside Reverse Transcriptase Inhibitors.
• The combination treatment is known as Highly
Active Anti-Retroviral Therapy (HAART).
 Highly Active Anti-Retroviral Therapy
(HAART)

• A typical HAART combination would involve :

- two nucleoside reverse transcriptase

inhibitors with
- either a non-nucleoside reverse transcriptase
inhibitor or one or two protease inhibitors.
 Nucleoside RTIs
• This class includes:
• Zidovudine (AZT)
• Abacavir (ABC)
• Lamivudine (3TC)
• Didanosine (ddI)
• Zalcitabine (ddC)
• Stavudine (d4T)
• HAART regimens are often given only by a list
of these abbreviations.
 Non-nucleoside RTIs
• These are chemically diverse compounds that
bind to the reverse transcriptase near the
catalytic site and denature it.
• Most of them are inducers, substrates or
inhibitors to varying degrees of the liver
cytochrome P450 enzymes.
• Current available drugs include:
• Efavirenz (EFZ)
• Nevirapine (NVP)
 PROTEASE INHIBITORS
• They affect the protein portion of the virus, not
the nucleic acid portion.
• They inhibit the ability of the virus to organize
its proteins prior to carrying out additional cell
infection. Current ones include:
- Saquirnavir (SQV)
- Nelfinavir (NFV)
- Indinavir (IDV)
- Ritonavir (RTV)
- Amprenavir (AMP)
 ANTIHELMINTHIC DRUGS
• Humans are the primary hosts for most
helminth infections, i.e most worms produce
sexually in the human host, producing eggs or
larvae that pass out of the body and infect a
secondary host.
• There are two clinically important types of
worm infestations:
- Those in which the worms live in the host’s
alimentary canal.
- Those in which the worm lives in other tissues
of the host’s body.
 WORMS THAT LIVE IN THE HOST’S
ALIMENTARY CANAL
• Main examples of worms that live in the host’s
alimentary canal are:
• Tapeworms – Taenia saginata, Taenia sohum,
etc.
• Intestinal round worms (nematodes):
Enterobius vermicularis - threadworm (called
pin worm in the U.S.A); Ankylostoma
duodenale (hookworm), etc.
WORMS THAT LIVE IN THE TISSUES OF THE
HOST
• Main examples of worms that live in the
tissues of the host:
- Trematodes or flukes eg. Schistosoma
haematobium, Schistosoma mansoni, etc.
They cause Schistosomiasis (bilharzia).
- Tissue round worms: Trichinella spiralis,
Dracunculus medinenesis (guinea worm).
 ANTIHELMINTIC DRUGS
• Benzimidazoles: eg.Mebendazole,
Thiabendazole, Albendazole.
• Praziquantel.
• Piperazine.
• Pyrantel.
• Niclosamide.
• Oxamniquine.
• Diethyl Carbamazine.
• Levamisole.
 ANTINEOPLASTIC AGENTS
• These are chemotherapeutic agents used in
the treatment of cancer.

• They are also referred to as:

- anticancer,
- cytotoxic,
- oncolytic or
- carcinostatic agents.
 X’TICS OF CANCER
• Cancer is a collection of diseases characterized
by :
- malignant cells which multiply and
- proliferate in an unrestrained manner,
- invade adjacent tissues and
- disseminate to distant organs to
- form daughter colonies (secondary tumours).
 CAUSATIVE AGENTS OF CANCER
Main causative agents include:
• Certain chemicals eg. Poly aromatic
hydrocarbons.
• Radiant energy.
• Certain Viruses.
• Cellular mutation of unknown origin.
 CANCER TREATMENT
These are four major lines of
treatment:
• Surgery
• Radiation therapy
• Immunotherapy
• Chemotherapy with antineoplastic
agents
CATEGORIES OF ANTINEOPLASTIC AGENTS

• Biological Alkylating agents – they form covalent

bonds with DNA thereby impeding DNA
replication.
• Antimetabolites – they block one or more of the
metabolic pathways involved in DNA synthesis.
• Hormones. eg. Glucocorticoids.
• Cytotoxic antibiotics – they prevent mammalian
cell division.
• Plant products. Eg. vinca alkaloids, taxanes, etc.
• NB: Cancer cells and normal cells are so
similar in many respects that is more difficult
to find general exploitable, biochemical
differences between them. antimicrobial
chemotherapy.
 Biological Alkylating Agents
5 major types exist:

• Nitrogen mustards
• Alkyl sulphonates
• Ethylenimines
• Nitrosoureas
• Others
 Biological Alkylating Agents
Nitrogen mustards:
• They are mostly characterized by a bis-2-
chloroethylamine substituent.

• Mustine, where X = CH3 was the first of the

nitrogen mustard anticancer agents and the first
anticancer drug to win clinical approval.
 Biological Alkylating Agents
• Another example is Chlorambucil where X =
HOOCCH2CH2CH2-ph
 Biological Alkylating Agents
• Alkyl Sulphonates – A typical example is
Busulphan.
 Biological Alkylating Agents
• Ethylenimines – an example is thiotepa.
 Biological Alkylating Agents
• Nitrosoureas – an example is semustine
 THE ANTIMETABOLITES
for cancer treatment
These are compounds that:
• prevent the biosynthesis or utilization of
essential cellular metabolites through
• enzyme inhibition or by incorporation into
essential molecules to form false products and
• are usually closely related to the metabolite
that is antagonized.
 THE ANTIMETABOLITES
for cancer treatment

• They block normal metabolic process of the cell

by either replacing the endogenous metabolite or
inhibiting an enzyme.
• They inhibit a metabolic pathway essential for the
survival or reproduction of cancer cells through
- the inhibition of folate, purine, pyrimidine or
pyrimide nucleoside pathways required for DNA
synthesis,
- thus inhibiting cell growth. Eg. 5-fluorouracil, 6-
mercaptopurine.
 THE ANTIMETABOLITES
• 5-fluorouracil
 HORMONES
for cancer treatment
• Hormonal therapy for cancer was ushered in by
an observation that the presence or absence of
the male hormone testosterone influenced
prostatic growth and the growth of prostatic
cancer.
• It was later shown that breast cancer in women
before the menopause, is favourably influenced
by androgenic compounds; eg.
methyltestosterone,
• and in women beyond the menopause by
oestrogenic compounds; eg. diethyl stilboestrol.
 HORMONES
• Eg. Diethyl stilboestrol
 ANTIBIOTICS
for cancer treatment
• Several antibiotics have recently been
recognized as important antineoplastic drugs.
• They are derived from fungal species, usually
streptomyces, and have antibacterial activity.
• They owe their activity to intercalation with
DNA and appear to act as cell – growth
inhibitors.
• They include dactinomycin, bleomycins,
mitomycins.
 ANTIBIOTICS

• dactinomycin
 PLANT PRODUCTS
FOR CANCER TREATMENT
• Many plant species have been screened in
different parts of the world, especially at the
National Cancer Institute at Bethseda, USA, for
possible anticancer agents.
• Some of the chemical classes of compounds
which have been isolated and biologically
evaluated for antineoplastic activity include
the following:
 PLANT PRODUCTS
• Sesquiterpene lactones
• Diterpenes of the phorbol types
• Triterpenes of the Cucurbitacin and
Withanolide type.
• Lignans
• Monomeric and dimeric indole alkaloids.
• Isoquinoline alkaloids.
ANTISEPTICS AND DISINFECTANTS
• Antiseptics are agents that destroy or inhibit
the growth of microorganisms when applied
to living tissues.
• Most of them have a limited spectrum of
activity and may have adverse effect on
tissues.
• They are used extensively to destroy bacteria,
bacteria spores, fungi, viruses and protozoa in
local infections or infestations and to prepare
the skin for surgical procedures.
ANTISEPTICS AND DISINFECTANTS
• They belong to different chemical structures.
• Disinfectants are applied to inanimate objects;
they are bactericidal and rapidly produce an
irreversibly lethal effect.
ANTISEPTICS AND DISINFECTANTS
CLASSES :
• PHENOLS AND BIPHENOLS
• They have antiseptic, germicidal, antihelmintic, caustic
and protein precipitant properties. Eg.
-liquefied phenol,
-p-chlorophenol,
- hexachlorophene,
- cresol,
- thymol,
- eugenol,
- resorcinol,
ANTISEPTICS AND DISINFECTANTS
• The effectiveness of phenols is enhanced by
introducing electron withdrawing groups, such
as halogens as in hexachlorophene, which is
incorporated in soaps, creams, oils and other
vehicles for topical application.

• They owe their antiseptic action to protein

denaturation and coagulation.
ANTISEPTICS AND DISINFECTANTS
• ALCOHOLS
• They also have germicidal action due to
denaturing effect on proteins.
• Their main application as antiseptics is in
surgical procedures.
• Examples include:
- ethanol,
- chlorbutanol and
- propylene glycol.
ANTISEPTICS AND DISINFECTANTS
• ACIDS AND DERIVATIVES
• These include:
- acetic acid,
- boric acid,
- salicylic acid,
- the parabens (methyl, ethyl, propyl, butyl-p-
hydroxy benzoates) and
- sodium benzoates – these are used as
preservatives.
ANTISEPTICS AND DISINFECTANTS
• 8-HYDROXYQUINOLINES
• They are used for their antibacterial,
antiamoebic and antifungal activities.
• They have metal chelating ability and act via
their chelating property. Eg. Chloroxine
ANTISEPTICS AND DISINFECTANTS
HALOGENS AND HALOGEN CONTAINING
COMPOUNDS
• Iodine tincture and iodine solutions are used
for the treatment of wounds.

• Halazone is used to disinfect drinking water.

• Most of these compounds decompose in

water to form hypochlorous acid, which is
responsible for the germicidal activity.
ANTISEPTICS AND DISINFECTANTS
• MEDICINAL DYES
• Used typically for various skin infections.
• Main classes of medicinal dyes include:
• a) Acridine dyes. Eg. Proflavine
 MEDICINAL DYES
• b) Thiazine dyes. Eg. methylene blue
 MEDICINAL DYES
• c) Azo dye. Eg. Amaranth
 MEDICINAL DYES
• Triphenylmethane dyes. Eg. gentian violet.
 PHARMACODYNAMIC AGENTS
DRUGS ACTING ON THE CENTRAL NERVOUS
SYSTEM (CNS)
• Drugs that exert their primary effects
upon the central nervous system produce
specific physiological and psychological
effects. They can:
 PHARMACODYNAMIC AGENTS
• psychological effects. They can:
• Relieve pain
• Lower body temperature
• Suppress disorders of movement
• Prevent epileptic seizures
• Induce sleep or arousal
 PHARMACODYNAMIC AGENTS

• Reduce the desire to eat

• Allay the tendency to vomit
• Treat anxiety
• Treat mania
• Treat depression
• Treat schizophrenia
 PHARMACODYNAMIC AGENTS
• Modern surgery would be impossible
without general anaesthetics.
• Potent psychotherapeutic agents treat
mental illness.
• Socially acceptable stimulants and anti-
anxiety agents produce stability, relief
and even pleasure for many.
 PHARMACODYNAMIC AGENTS
• Addiction to some of these drugs
adversely affects lives.
• Before these agents can act on the CNS,
they must be able to pass through the
blood – brain barrier to the brain.
• The CNS has excitatory and inhibitory
chemical transmitters.
 PHARMACODYNAMIC AGENTS
• The most probable of them are:
• acetylcholine,
• adrenaline,
• noradrenaline,
• dopamine,
• serotonin,
• histamine,
• L-glutamic acid,
• γ-aminobutyric acid.
 CNS DRUGS
• Many drugs that modify the functions of the
CNS affect the concentration of one or more
of these substances in the CNS as well as the
peripheral nervous system.
• Apart from these neuro-chemical, several
endogenous peptides have been discovered in
the brain: these include:
enkephalin, endorphins, somatostatin,
gastrin, cholecystokinin, oxytocin.
 CNS DRUGS
• Drugs interfering with the release and action
of these endogenous peptides may produce
certain CNS effects.
.
 ANALGESICS
• It is difficult to define pain. Pain is both a
physiological and psychological phenomenon.
• Pain can be considered as acute or chronic.
• An acute pain is produced by disease, injury,
noxious chemicals or some physical
stimulations such as heat, etc.
• Chronic pain by its persistent and pathological
form appears to have no biological function. It
imposes physical, emotional and social stress
of severe magnitude
 ANALGESICS
• The human body produces its own pain
relievers
• They are known as enkephalins and they are
small polypeptides made in the brain
• Example is Methionine with formula
Try-Gly-Gly-Phe-Met
 ANALGESICS
• There are two major classes of analgesic
agents:
a) Mild analgesics which include
- antipyretic drugs,
- anti-inflammatory analgesics.

b) Strong analgesics which include

- narcotic analgesics and
- agonist – antagonist analgesics.
 ANALGESICS
• Analgesics are CNS depressants.
• They produce insensitivity to pain without loss
of consciousness.
• Naturally occurring analgesics are found
among the opium alkaloids, and are of two
main groups:
- The morphine group
- The papaverine group
ANALGESICS DERIVED FROM SALICYLIC
ACID O
C
OH

SALICYLIC ACID
OH
• It is the first pain reliever
Salicylic acid
• It was discovered in 1860
• IUPAC name is o-hydroxy benzoic acid
• It is antipyretic (lowers body temperature)
• It is also an analgesic
• It has a very sour taste because it is both phenolic
and an acid.
• It causes stomach irritation
 ANALGESICS DERIVED FROM SALICYLIC
ACID
• SODIUM SALICYLATE
O
C
ONa

OH

Sodium salicylate
• It is the sodium salt of salicylic acid
• It was introduced in 1875
• It tastes less bitter
• It causes stomach irritation and other
problems
 ANALGESICS DERIVED FROM SALICYLIC
ACID
• PHENYL SALICYLATE O
C
OC6H5

OH

Phenylsalicylate

• It is the phenyl ester of salicylic acid

• It was introduced in 1886
• It was found to be an improvement upon the first two since it did
not hydrolyze into salicylic acid and phenol until it reached the
intestines
O O
• It solved the stomach
C irritation problem C
OH O
+ OH

OH OH
 ANALGESICS DERIVED FROM SALICYLIC
ACID
O
• ACETYL SALICYLIC ACID
C
• It is also known as ASPIRIN OH
O
O C
CH3
Acetyl salicylic acid
• It works by reducing the body’s prostaglandin levels
• Prostaglandins cause the pain associated with fever,
swelling and menstruation
• Aspirin thus relieves pain
 ANALGESICS DERIVED FROM SALICYLIC
ACID
• METHYL SALICYLATE C
O

O CH3

OH

Methyl salicylate

• It is the most common topical (external)

analgesic
• It is used in rubbing creams and balms but not
ingested
• It is not ingested because when it hydrolyses,
methanol is produced which is poisonous.
 ANALGESICS DERIVED FROM ANILINE
(Aminobenzene)
1. ACETANILIDE
• Produced from a reaction of aniline with
ethanoyl chloride
O
NH2
O NH C
CH3
+ Cl C
CH3
 ANALGESICS DERIVED FROM ANILINE
(Aminobenzene)
2. PARACETAMOL
• It is the phenolic derivative of acetanilide
• It is produced from a reaction of acetanilide with
water.
O
O
NH C
CH3 NH C
CH3
+ H2O

OH
p-hydroxyacetanilide
 ANALGESICS DERIVED FROM ANILINE
(Aminobenzene)
3. PHENACETIN
• It is produced through ethylation of the
hydroxyl hydrogen (phenolic –OH)
• Structure
O
NH C
CH3

OCH2CH3
ANALGESICS DERIVED FROM ACETIC ACID

DICLOFENAC
Structure

CH2COOH

Cl
NH
Cl
 ANALGESICS DERIVED FROM ARYL
PROPANOIC ACID
H3C HC COOH
1. IBUPRUFEN

CH2CH(CH3)2
Ibuprufen
2. NAPROXEN H3C HC COOH

H3CO
Naproxen
 NARCOTIC ANALGESICS (NATURAL AND
SYNTHETIC OPIODS)
• These are more potent analgesics which are
only available on prescription
• Narcotic analgesics or opiods exert their
therapeutic effects by mimicking naturally
occurring substances termed
- endogenous opiod peptides or
- endorphins at opiod receptors.
NARCOTIC ANALGESICS (NATURAL AND SYNTHETIC OPIODS)

• They are conveniently divided into 5 groups

1. Morphine and related substances
 NARCOTIC ANALGESICS
2. Morphinans
 NARCOTIC ANALGESICS
3. 6, 7-Benzomorphans
 NARCOTIC ANALGESICS
4. Phenylpiperidines
 NARCOTIC ANALGESICS
5. Diphenylpropylamines
 MORPHINE AND RELATED SUBSTANCES

• The morphine molecule can be altered in a

variety of ways. The various derivatives
include:
• Methyl morphine or codeine: methylation of
the phenolic hydroxyl group or morphine.
 MORPHINE AND RELATED SUBSTANCES
• Dimethyl morphine or Thebaine: methylation of
both hydroxyl groups of morphine.
H3CO

O N

H
H3CO

Dimethyl morphine (Thebaine)

• Diacetylmorphine or Heroin: acetylation of both

alcoholic and phenolic hydroxyl groups of
morphine. H3CH2CO

O N

H
H3CH2CO

Diacetylmorphine or Heroin
MORPHINE AND RELATED SUBSTANCES
• Codeine
H3C

CH3
O N

H
HO

CODEINE
 MORPHINE AND RELATED SUBSTANCES
• Dihydromorphinone or Dilaudid: oxidation of the
alcohol hydroxyl group to a ketone and reduction
of the C7 – C8 double bond.
HO

O N

H
O

DIHYDROMORPHINONE
 MORPHINE AND RELATED SUBSTANCES
• Methyl dihydromorphinone or Hydrocordone or
metopon: conversion of the phenolic hydroxyl
group of dihydromorphinone to methoxy group.
H3CO

CH3
O N

H
O

METHYLDIHYDROMORPHINONE
ABUSE OF NARCOTIC ANALGESICS

• Abuse of narcotic analgesics is characterized

by psychic and physical dependence, as well as
tolerance.
STEROIDAL ANALGESICS (Corticosteroids)

• They are used to relieve pain and control

inflammation in rheumatoid arthritis

• They are drugs of second choice, they are

used when other anti-inflamatory agents have
failed
• Examples are Cortisone, prednisone,
dexamethasone
 STEROIDAL ANALGESICS (Corticosteroids)

• Cortisone O
HO

H
HO

H H

O
cortisone
STEROIDAL ANALGESICS (Corticosteroids)

• Prednisone O
HO

H
HO

H H

O
prednisone

17,21-dihydroxypregna-1,4-diene-3,11,20-trione
 ANTIDEPRESSANT DRUGS
• A depressed person / patient has feelings of
helplessness, hopelessness and worthlessness.
• They often think of suicide
• Examples are the monoamine oxidase inhibitors
(MAOI)- Phenelzine

CH2CH2NHNH2
 HALLUCINOGENIC AGENTS
• They are also psychotomimetic /psychedelic agents
• The major groups of hallucinogenic groups are
Indolalkylamine
• Example: Lysergic acid diethyl amide (LSD)
O

C2H5 N C

N CH3
C2H5

N
 CANNABINOIDS
• The indin hemp plant is a variety of cannabis
sativa, family cannabaceae
• It is found wild in India, Pakistan, and
Bangladesh
• There are three distinct species:
- cannabis indica
- cannabis ruderalis
- cannabis sativa
 CANNABINOIDS
• Three main types of narcotics produced from
hemp
- Indian hemp / ganja
- Bhang or Hashish
- Charas or chahrruhs
• Ganja is mostly the leaves, fruits or stem
• Hashish is mainly the twigs and resins
 CANNABINOIDS
• General formula
CH2R

OH

R1 R2

• Cannabinol: R=R1=R2=H
 CNS STIMULANTS
• There are two main groups:
- General stimulants/ Analeptics
- Psychic / cerebral stimulants
• Examples include Xanthine derivatives
- Caffeine, theophylline, and theobromine
O
CH3

N
H3C N

N
O N
CAFFEINE
CH3
 CNS STIMULANTS
• Theophylline
 CNS STIMULANTS
• Theobromine
 CARDIO-VASCULAR AGENTS

• Cardio-vascular diseases comprise of

a) heart diseases

b) diseases of blood vessels

c) diseases of the lymphatic vessels

 CARDIO-VASCULAR AGENTS
1. CARDIOTONICS
• They are agents that increase the contractile force
of the heart.
• They include cardiac glycosides
X
CH3 O

OH

(sugar groups) RO
 CARDIO-VASCULAR AGENTS
2. ANTIARRHYTHMIC DRUGS
• They are used in the treatment of disturbances
of the heart rate and rhythm.
Example: Quinidine
 CARDIO-VASCULAR AGENTS

Xylocaine / Lignocaine
 CARDIO-VASCULAR AGENTS
3. ANTI-HYPERTENSIVE AGENTS
• For normal blood pressure, systolic is less than
or equal to 140 and diastolic is less than or
equal 90.
• Ideal blood pressure is 120/80 mmHg
• Above 160 a person is considered
hypertensive
• Some of the agents/drugs are
 CARDIO-VASCULAR AGENTS
• Nifedipine
 CARDIO-VASCULAR AGENTS

RESERPINE
 CARDIO-VASCULAR AGENTS

ATENOLOL
 CARDIO-VASCULAR AGENTS

PROPRANOLOL

(RS)-1-(1-methylethylamino)-3-(1-naphthyloxy)propan-2-ol
 ANTI-ANGINAL DRUGS
• Angina pectolis is characterized by a severe
contracting pain in the chest.

• Main drugs includes nitrates (R-O-N=O)

Eg. Nitroglycerine
 ANTI-ANGINAL DRUGS

Nitroglycerine
 PSYCHOTHERAPEUTIC AGENTS
1. ANTI-PSYCHOTIC AGENTS
• They are also referred to as Neuroleptics or
Tranquilizers
• Eg. Reserpine

N
OCH3

O OCH3
N
H3CO
OCH3
H3C C OCH3
O
 PSYCHOTHERAPEUTIC AGENTS
• PROMETHIAZINE
S

NH

CH2CHN(CH3)2

CH3
 PSYCHOTHERAPEUTIC AGENTS
2. ANTI-ANXIETY AGENTS
• They are also called Anxiolytic or Minor tranquilizers
• The main classes are the Benzodiazepines,
Diazepam or valium O

N
N

Cl
valium
 LETHAL DOSE (LD50) VALUES OF
CHEMICALS/DRUGS
• LD50 is a measure of toxicity and it is the
amount of drug/chemical that causes death of
50% of laboratory animals in a toxicity test.
• It is usually expressed as mg/kg of the body
weight
• The higher the LD50 value the safer the
chemical and vice versa
 LETHAL DOSE (LD50) VALUES OF
CHEMICAL/DRUGS

Lethal Dose (LD50) g/Kg of mice

Ethanol 10.6
Aspirin 1.1
Paracetamol 0.3
NaCN 0.02
 VITAMINS
• They are trace organic substances required in
a diet
• They are essential for normal metabolism in
living things
• Many are precursors of co-enzymes
• They are generally classified into two groups
- Fat Soluble (A, D, E and K)
- Water Soluble (B and C)
 FAT (LIPID) SOLUBLE VITAMINS
VITAMIN A
• It is a diterpenoid
CH3 CH3 CH3

CH2OH

CH3

CH3

(2E, 4E, 6E, 8E)-3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)

-2,4,6,8-nonatetraen-1-ol
 FAT (LIPID) SOLUBLE VITAMINS
• Vitamin A promotes growth
• It prevents night blindness and promotes
health of the skin
 FAT (LIPID) SOLUBLE VITAMINS
• Vitamin D

HO

Vitamin D
 FAT (LIPID) SOLUBLE VITAMINS
• VITAMIN D2
 FAT (LIPID) SOLUBLE VITAMINS
• VITAMIN D3
 FAT (LIPID) SOLUBLE VITAMINS
• VITAMIN D4
 FAT (LIPID) SOLUBLE VITAMINS
• VITAMIN K
O

Vitamin K
FAT (LIPID) SOLUBLE VITAMINS
 WATER SOLUBLE VITAMINS
• VITAMIN B1 - THYAMINE

3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)- 5-(2-hydroxyethyl)-4-methylthiazolium chloride

 WATER SOLUBLE VITAMINS
• VITAMIN B2 – RIBOFLAVIN

7,8-Dimethyl-10-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]benzo[g]pteridine-2,4-dione[1]
 WATER SOLUBLE VITAMINS
• VITAMIN B6 - Pyridoxal phosphate
 WATER SOLUBLE VITAMINS
• VITAMIN B12 – Cyanocobalamin

6-dimethylbenzimidazolyl)cobamidcyanide
 WATER SOLUBLE VITAMINS
• VITAMIN C – Ascorbic acid

OH HO
HO

O OH
O
ASCORBIC ACID
 HORMONES
A) STEROIDAL HORMONES
• Cholesterol is the precursor f the steroidal
hormones
• Cholesterol occurs in most body tissues, 10%
of it occurs in the brain
• The body synthesizes cholesterol if its supply
drops too low
• There are five main steroidal hormones
 HORMONES
• ESTRADIOL
 HORMONES
• Estradiol (abbreviated as E2), or 17β-estradiol,
also known as estra-1,3,5(10)-triene-3,17β-diol,
• It is a steroid and estrogen sex hormone, and
the primary female sex hormone.
• It is named for and is important in the regulation
of the estrous andmenstrual female
reproductive cycles.
• Estradiol is essential for the development and
maintenance of female reproductive tissues
 HORMONES
• It also has important effects in many other tissues
including bone.
• While estrogen levels in men are lower compared to
women, estrogens have essential functions in men as
well.
• Estradiol is found in most vertebrates as well as many
crustaceans, insects, fish, and other animal species
• Estradiol is produced especially within the follicles of
the female ovaries, but also in other endocrine (i.e.,
hormone-producing) and non-endocrine tissues (e.g.,
including fat, liver, adrenal, breast, and neural tissues).
 HORMONES
• PROGESTERONE
 HORMONES
• Progesterone (P4) is an endogenous
steroid and progestogen sex hormone
involved in the menstrual cycle,
pregnancy, and embryogenesis of
humans and other species.
• It belongs to a group of steroid
hormones called the progestogens.
• It is the major progestogen in the body.
 HORMONES
• Progesterone is also a crucial
metabolic intermediate in the production
of other endogenous steroids, including
the sex hormones and the corticosteroids
,
• It plays an important role in brain
function as a neurosteroid.[12]
• It is produced in the ovaries.
 HORMONES
• TESTOSTERONE
 HORMONES
• Testosterone is a steroid hormone.
• Testosterone is made primarily by the testicles
in males.
• Small amounts are also made by the
adrenal glands and the ovaries in females.
• In males it is the main sex hormone and plays
an important role in the development of the
male reproductive system.
 HORMONES
• In adult males it promotes
secondary sexual characteristic including
increased muscle growth and body hair.

• Levels of testosterone are typically more than

five times higher in adult males than females.
 HORMONES
• As a medication it is used to treat male
hypogonadism and certain types of
breast cancer.
• It may also be used to increase athletic ability
in the form of doping.
• It is unclear if the use of testosterone for
low levels due to aging is beneficial or
harmful.
• Testosterone can be used as a cream applied
to the skin, by injection into a muscle, or be
placed in the cheek.[1]
 HORMONES
• CORTISONE
 HORMONES
• Cortisone ( 17-hydroxy-11-
dehydrocorticosterone) is a 21-carbon
steroid hormone.
• It is one of the main hormones released by the
adrenal gland in response to stress.
• In chemical structure, it is a corticosteroid closely
related to cortisol.
• Cortisone, a glucocorticoid, and adrenaline are
the main hormones released by the body as a
reaction to stress. They elevate blood pressure
and prepare the body for a fight or flight response
 HORMONES
• It is used to treat a variety of ailments and can
be administered intravenously, orally,
intraarticularly (into a joint), or
transcutaneously.
• Cortisone suppresses the immune system,
thus reducing inflammation and attendant
pain and swelling at the site of the injury.
 HORMONES
• ALDOSTERONE
 HORMONES
• Aldosterone is a steroid hormone, "the main
mineralocorticoid hormone",
• It is produced by the outer section (zona glomerulosa
) of the adrenal cortex in the adrenal gland
• It plays a central role in the regulation of the
plasma sodium (Na+), the extracellular potassium (K+)
and arterial blood pressure.
• It does so mainly by acting on the distal tubules and
collecting ducts of the nephron, increasing
reabsorption and excretion of ions out of and into the
tubular fluids of the kidney.
 HORMONES
B) POLYPEPTIDE HORMONES
• INSULIN
 HORMONES
• Insulin (from the Latin, insula meaning
island) is a peptide hormone produced by
beta cells of the pancreatic islets.
• It is also produced by the Brockmann body in
some teleost fish.
• It has important effects on the metabolism of
carbohydrates, fats and protein by promoting
the absorption of, especially glucose from the
blood into fat , liver and skeletal muscle cells.
 HORMONES
• In these tissues the absorbed glucose is
converted into either :
- glycogen via glycogenesis or
- fats (triglycerides) via lipogenesis, or,
- in the case of the liver, into both.
• Glucose production (and excretion into the
blood) by the liver is strongly inhibited by
high concentrations of insulin in the blood.
• Circulating insulin also affects the synthesis
of proteins in a wide variety of tissues.
 HORMONES
• In high concentrations in the blood it is
therefore an anabolic hormone, promoting
the conversion of small molecules in the blood
into large molecules inside the cells.
• Low insulin levels in the blood have the
opposite effect by promoting widespread
catabolism.
 HORMONES
MELANOCYTE STIMULATING HORMONE (MSH)

TYPE OF MSH: AMlNO ACID SEQUENCE

Ala-Glu-Lys-Lys-Asp-Glu-Gly-Pro-Tyr-Arg-Met-Glu-His-
β-MSH (human):
Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp

Asp-Glu-Gly-Pro-Tyr-Lys-Met-Glu-His-Phe-Arg-Trp-Gly-
β-MSH (porcine):
Ser-Pro-Pro-Lys-Asp

γ-MSH: Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly

α-MSH: Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val
 HORMONES
• The melanocyte-stimulating hormones,
known collectively as MSH, also known as
melanotropins or intermedins,
• They are a family of peptide hormones and
neuropeptides of α-melanocyte
-stimulating hormone (α-MSH),β-melanocyte
-stimulating hormone (β-MSH), and γ-
melanocyte-stimulating hormone (γ-MSH).
• They are produced by cells in the
intermediate lobe of the pituitary gland.
 HORMONES
• MSH stimulate the production and release of
melanin (a process referred to as
melanogenesis) by melanocytes in skin and hair.
• MSH actions in the brain have effects on
appetite and sexual arousal.
• An increase in MSH will cause darker skin in
humans.
• MSH increases in humans during pregnancy.
This, along with increased estrogens, causes
increased pigmentation in pregnant women.
 HORMONES
• HUMAN GROWTH HORMONE (HGH)
 HORMONES
• Growth hormone (GH) is also known as
somatotropin (or as human growth hormone
[hGH or HGH] in its human form).

• It is a peptide hormone that stimulates growth

, cell reproduction, and cell regeneration in
humans and other animals.

• It is thus important in human development.

 HORMONES
• It is a type of mitogen which is specific only to
certain kinds of cells.
• Growth hormone is a 191-amino acid, single-
chain polypeptide that is synthesized, stored,
and secreted by somatotropic cells within the
lateral wings of the anterior pituitary gland.
• GH is a stress hormone that raises the
concentration of glucose and free fatty acids.
• It stimulates production of IGF-1.
 HORMONES
THYROID STIMULATING HORMONE
• Thyroid-stimulating hormone (also known as
thyrotropin, thyrotropic hormone, TSH, or hTSH for
human TSH)
• It is a pituitary hormone that stimulates the thyroid
gland to produce thyroxine(T4), and then
triiodothyronine (T3) which stimulates the metabolism
of almost every tissue in the body.[1]
• It is a glycoprotein hormone synthesized and secreted
by thyrotrope cells in the anterior pituitary gland, which
regulates the endocrine function of the thyroid.
HORMONES
 HORMONES
• TSH stimulates the thyroid gland to secrete the
hormone thyroxine (T4), which has only a slight
effect on metabolism.
• T4 is converted to triiodothyronine(T3), which is
the active hormone that stimulates metabolism.
• About 80% of this conversion is in the liver and
other organs, and 20% in the thyroid itself.
• TSH is secreted throughout life but particularly
reaches high levels during the periods of rapid
growth and development.
 HORMONES
• The hypothalamus, in the base of the brain,
produces thyrotropin-releasing hormone
(TRH). TRH stimulates the pituitary gland to
produce TSH.
• Somatostatin is also produced by the
hypothalamus, and has an opposite effect on
the pituitary production of TSH, decreasing or
inhibiting its release.
 HORMONES
(S)-triiodothyronine (T3, also called liothyronine in
the pharmaceutical industry
 HORMONES
• TYROXINE (T4)

(S)-thyroxine (T4.)
 HORMONES
• PARATHYROID HORMONE
 HORMONES
• OXYTOCIN
 HORMONES
• Oxytocin is normally produced by the
paraventricular nucleus of the hypothalamus
and released by the posterior pituitary.

• It plays a role in social bonding,

sexual reproduction in both sexes, and during
and after childbirth.
 HORMONES
• Oxytocin is released into the bloodstream as a
hormone in response to stretching of the
cervix and uterus during labor and with
stimulation of the nipples from breastfeeding.

• This helps with birth, bonding with the baby,

and milk production
 HORMONES
• PROLACTIN
 HORMONES

• It is also known as luteotropic

hormone or luteotropin,
• It is a protein that in humans is best known
for its role in enabling
mammals, usually females, to produce milk.
• It is influential in over 300 separate processes
in various vertebrates.
 HORMONES
• Prolactin is secreted from the pituitary gland
in response to eating, mating, estrogen
treatment, ovulation and nursing.
• Prolactin is secreted in pulses in between
these events.
• Prolactin plays an essential role in metabolism,
regulation of the immune system and
pancreatic development.