Medicinal Chemistry – III

( semester Exam)

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 Unit 1st
Q. 1 ) Define, Classify Beta lactam Antibiotics. Write in detail note on penicillin
(10 mark)
Ans:-
I) Antibiotics
• The drug which are made up from microorganisms to kill another type of
microorganism know as antibiotics

II) Beta Lactam Antibiotics

• β-lactam antibiotics are antibiotics contain Beta-lactam ring in their
chemical structure
• The drugs which are made up from Microorganisms to kill another type of
microorganisms such drugs are known as antibiotics
• Example :- penicillin , cephalosporin

III) Classification of Beta lactam antibiotics

IV) Penicillin

A) History
• In 1928 Alexander Fleming
- Accidentally found penicillin
• In 1930 Florey and Co-worker
- Isolated compound
- By freeze drying process
- From fungus strain
- And name it penicillin

• In 1945 D. Hodgkin
- Explain structure of penicillin

• In 1957 Sheehan
- Develop synthetic route for production of penicillin

B) General structure of Penicillin

C) Nomenclature Of Penicillin
1) As per Chemical Abstract
• 6-acylamino-2, 2- dimethylpenam-3-Carboxylic acid
2) As per USP
• 4-thia-1-azabicyclo heptane
D) Mechanism of Action
• Inhibit cell wall synthesis
• Bind with Transpeptidase enzyme
• Prevent binding of adjacent glycan chain
E) Stereochemistry
• The absolute stereochemistry of penicillin is designed as 3S:5R:6R

F) Amoxicillin

• Properties
- White or almost white
- Hygroscopic powder
- Very Soluble in water
- Very slightly soluble in acetone
- Store in air tight container
- Protected from light

• MOA
- Inhibit cell wall synthesis
- Bind with Transpeptidase enzyme
- Prevent binding of adjacent glycan chain

• Uses
- Skin infection
- Sinusitis
- Urinary tract Infections
Q. 2) Explain SAR OF penicillin (5mark)
Ans:-
I) SAR of penicillin

A) R-Group

1) Bulky groups provide resistance to B-lactamase

2) Polar groups make structure more hydrophilic
3) Hydrophilic groups make structure more active against Gram -
ve than Gram +ve
4) Hydrophobic groups make structure more active against Gram
+ve than Gram-ve

B) Carbonyl Oxygen.

1) = 0 is ready for nucleophilic attack So, oxygen increase

stability and activity
C) Carboxylic group

1) Carboxylic group is important for activity.

2) Carboxylic group mostly active in sodium of potassium ionized
salt.
3) Modification at this group reduce activity.

D) Stereochemistry

1) CIS-stereochemistry is essential for maximum activity

E) Beta- lactam Ring

1) Beta- lactam ring is essential for antibacterial action.

Q. 3) Explain In Detail About tetracycline ( 10 Mark)
Ans:-
I) Tetracycline Antibiotics
• Broad Spectrum Antibiotics
• Treat wide variety of infection
• Inhibit Growth Of Bacteria by inhibiting translation process

II) General structures of tetracycline

III) History
• In 1940 Benjamin Minge Dagger
- Identified tetracycline as a therapeutic substances produces by soil
microorganisms
IV) Classification Of tetracycline
A) According to Source
Natural Source Semi-synthetic Source
• Oxytetracycline • Methacycline
• Demeclocycline • Doxycycline
• Chlortetracycline • Minocycline
• Tetracycline • Meclocycline

B) According to substitution on various carbon atom

R1 R2 R3 R4
1.Tetracycline H OH CH3 H
2.Chlortetracycline Cl OH CH3 H
3.Oxytetracycline H OH CH3 O

V) Mechanism Of Action
• Inhibit Bacterial protein synthesis
• Bind with 30S Ribosomal subunit
• prevent binding of aminoacyl tRNA to mRNA Complex
• Terminate translation process
VI) Official Drugs
A) Tetracycline
B) Chlortetracycline

A) Tetracycline

1) Properties
- Yellow Crystalline Powder
- Very Slightly soluble in water
- Sparingly soluble in acetone
- 1% suspension in water has pH 3.5 to 6.0
- Store in air tight container
- Protected from light
2) MOA
- Inhibit Bacterial protein synthesis
- Bind with 30S Ribosomal subunit
- prevent binding of aminoacyl tRNA to mRNA Complex
- Terminate translation process
3) Use
• use in treatment of
- Gonorrhoea
- Respiratory tract infections
- ear infection

B) Chlortetracycline

1) Properties
- Yellow odourless crystalline powder
- practically insoluble in acetone , ether
- soluble in solution of alkali hydroxide and carbonate
- 1 % suspension in water has 2.3 to 3.3
- store in air tight container
- protected from light
2) MOA
- Inhibit Bacterial protein synthesis
- Bind with 30S Ribosomal subunit
- prevent binding of aminoacyl tRNA to mRNA Complex
- Terminate translation process

3) Use
• Use in treatment of
- Respiratory tract infections
- sinuses
- middle ear infection
- skin infection
- otitis media
Q. 4 Explain SAR of Tetracycline
Ans :-
I) SAR Tetracycline
Q. 5) Write in short on Beta-lactamase inhibitor ( 5Mark)
Ans :-
I) Beta Lactamase enzyme Inhibitor
• Beta-lactamase inhibitors are drugs that are co-administered with beta-lactam
antibiotics
• it prevent antibacterial resistance by inhibiting beta-lactamases
• protect beta lactam antibiotics
• Example :-
1) Sulbactam
2) Tazobactam
3) Clavulanic Acid

II) Sulbactam

A) Properties
• White to off white crystalline powder
• Freely soluble in water and dilute acid
• sparingly soluble in acetone , chloroform
 • store in air tight container
• protect from light
B) Characteristics
• Broad Spectrum
• Intravenous
• Resistance to Beta-lactamase enzymes
C) Mechanism of Action
• Bind with Beta Lactamase
• Protect antibiotics from destruction
D) Uses
• Treat Urinary tract infections
• Treat Respiratory tract infections
• treat Sinusitis

Q.6) Define Antibiotics ? Explain classification of Beta lactam compounds.

Ans:-
I) Antibiotics
• The drugs which are made up from microorganisms to kill another type of
microorganisms such drugs are Known as antibiotics
• The drugs which are use to kill Microorganism or inhibit the growth of
microorganisms such drugs are known as antibiotics

II) Classification of Beta lactam Compound

• Beta-lactam compounds are classified into four types

 A) Saturated five member rings

B) Unsaturated five member rings

C) Unsaturated six member rings

D) Beta-lactam not fused with any other ring

A) Saturated five member rings

• Saturated five member rings further classified into three types

B) Unsaturated five member rings

• Unsaturated five member rings further classified into two type

 C) Unsaturated six member rings

• Unsaturated six member rings further classified into three types

D) Beta-lactam ring note fuse with any other ring

1) Aztraonam
 Unit :- II

Q. 7) Explain In Detail About Macrolide Antibiotics ( 5 mark)

Ans :-
I) Macrolide Antibiotics
• Macrolide are class of antibiotics which are characterized by having lactone ring
structure
• Having Bacteriostatic effect on bacteria
• Use Instead of penicillin and Cephalosporin
• High tissue penetration
• Antimicrobial activity

II) Classification Of Macrolide Antibiotics

III) Chloramphenicol
• First Isolated From Streptomyces venezuelae in 1947
• It was first antibiotic made by synthesis
A) Properties
• white to greyish-white or Yellowish-White fine crystalline powder
• odourless and bitter in taste
• freely soluble in water
• Soluble in alcohols
• metabolized in liver
• Store in air tight container
• protected from light

B) Mechanism of Action
• Bind with 50 S Ribosomal subunit
• prevent formation of peptide bond
• inhibit protein synthesis

C) Uses
• use in treatment of
- H. Pylori infection
- Duodenal ulcer
- Meningitis
-Bacterial infection
Q.8 ) Explain In Detail About Antimalarial Agent ( 5 or 10 mark)
Ans:-

I) Antimalarial Agent
• The drug which are use to treat or to prevent malaria such drugs are known
As antimalarial agents.
• Antimalarial are type of Anti-parasitic chemical agent

II) Etiology of malaria

• Malaria is caused by plasmodium Species.
• Five major Plasmodium Species
I. Plasmodium Falciparum
II. Plasmodium Vivax
III. Plasmodium ovale
IV. Plasmodium malariae
V. Plasmodium knowlesi
• Plasmodium Falciparum is responsible for most severe disease
• Malaria transmitted in humans through a bite of female anopheles mosquito
III) Malaria Life Cycles
IV) Classification
1) 4- Aminoquinolines :- Chloroquine , Hydroxychloroquine
2) 8- Aminoquinolines :- Pentaquine , Iso-pentaquine
3) 4- quinolinemethanols :- Quinine , Quinidine
4) Phenanthrene methanol :- Halofantrine
5) Antibiotics :- Tetracycline , Doxycycline , Minocycline

V) Chloroquine

A) Properties
• white to slightly yellow crystalline powder
• Odorless and bitter in taste
• Very Slightly soluble in water
• Insoluble in alcohol and benzene
• metabolized in liver
• store in air tight container
• protected from light
B) Synthesis of Chloroquine
• It is prepared from reaction of 4-amino-7-chloroquinoline and 4-chloro-N, N-
diethylpentan-1-amine

C) Mechanism Of Action
• Bind with nucleoproteins and interfere with protein synthesis
• inhibit both RNA and DNA polymerase
• interfere with parasite ability to metabolize and utilize erythrocyte hemoglobin

D) Use
• Use in treatment of malaria
• use in treatment of acute and chronic rheumatoid arthritis
• use in treatment of amoebic liver abscess
VI) Pamaquine

#_ Properties, MOA And Use ( Same lihaych ithe chloroquine sarkh)

Q.9) What is prodrug ? Give it’s objectives. Explain Ideal properties of prodrugs
and Carrier and Give its Classification.
Ans:-
1) Prodrug

A pharmacologically inactive Compound that are Converted to an active drug

by a metabolic biotransformation.

2) Objectives.
A) pharmaceutical objective
• To improve water or Lipid Solubility
• To improve chemical stability
• To alter organoleptic properties.
• To decrease irritation and pain At injection site.
B) Pharmacokinetic objective
• To improve absorption.
• To reduced pre-systemic metabolism
• To increase organ/ tissue-selectivity.
C) Pharmacodynamics Objective.
• To decrease toxicity
• To improve therapeutic index.

3) Ideal properties of prodrug

1) The linkage between drug and Carrier Should be Covalent bond.

2) The prodrug should be inactive and Less active than parrent drug.
3) The linkage should be Bioreversible
4) The prodrug and the carrier released After enzymatic or non-enzymatic attack
should be not toxic.
5) The generation of active form must take place with rapid kinetics to ensure
effective drug level at site of action

4) Ideal properties of Carrier

1) Carrier should be without intrinsic toxicity.
2) Should be non immunogenic and non -antigenic
3) should not be accumulate in the body
4) It should posses a suitable number of functional group for drug attachment
5) It should be stable to chemical manipulation and autoclaving..
6) Should be easy to characterize
7) In mutual prodnig approach, the Carrier should have some biological activity of
its own.

V) Classification of prodrugs
prodrug are broadly classified into two type

A) Carrier linked prodrugs.

B) Bioprecursor prodrugs.

A) Carrier linked prodrugs.

• The promoiety is covalently linked to active drug, and it can be easily

cleaved by enzymes or non- enzymatically to give parent drug.
• The Carrier – linked prodrug Consists attachment to Carrier group and active
drug moiety
• The pro-moiety change physicochemical properties of drugs.
• The carrier should be non-immunogenic. and easy to synthesize.
• In Carrier-linked prodrugs pro-moieties are ester , amides, phosphates,
oximes.
• Carrier linked prodrug are Classified into four Categories
i)Double prodrugs
ii) site specific prodrug
iii) Macromolecular prodrug
iv) Mutual prodrugs

B) Bioprecursor prodrug
• In Bioprecursor prodrug there is no linkage to a Carrier or Pro-moiety
• Modification of Active drug take place itself.
• The Bioprecursor prodrug totally depends upon metabolism to introduce active
functional group
Q. 10) Give application of prodrugs. Various applications of prodrugs are as
Follows.
Ans:-
1) To improve taste of the drug
2) To improve odour of the drug
3) To increase bioavailability of the drug
4) To provide site specific drug delivery
5) To prolong duration action
6) To minimize toxicity
7) To protect from pre-systemic metabolism
8) To improve chemical stability of drug
9) To reduce pain at infection site
10) protection from rapid metabolism and excretion
11) To reduced toxicity
12) To increase lipid solubility of drug
 Unit-III
Q. 11) Explain in details About Anti-tubercular Agents
Ans:-
I) Anti-tubercular Agent

• The Drugs which are use to treat tuberculosis such drugs are known as
Anti-tubercular Agent
• Tuberculosis is infectious disease caused by Mycobacterium
• Two types of tuberculosis
1) Latent Tuberculosis
2) Active Tuberculosis

II) Classification of Anti-tubercular Agent

III) Isoniazid
A) IUPAC Name
• Pyradine-4-carbohydrazide
B) Properties
• Odourless colourless or white crystalline powder
• Slightly sweet at first and then bitter in taste
• soluble in water and alcohol
• Insoluble in ether and benzene
• Metabolized in liver
• Store in air tight container
• Protected from light
C) Mechanism of action
• Antimicrobial agent
• Block synthesis of mycolic acids
• Only active against active Mycobacterium
• It is prodrugs
• Interfere with metabolism of vitamin B6 in Mycobacterium
D) Synthesis

E) Use
• Treat tuberculosis
• Treat latent and active tuberculosis
• Treat Mycobacterium avium complex
Q. 12) Explain SAR of Quinolines
Ans :-
• SAR of Quinolines

1) 1,4-dihydro-4-oxo-3-pyridine carboxylic acid moiety is essential for

Antibacterial Activity .
2) Prototype drug in this category is Nalidixic acid.

3) Side chain of Nalidixic acid to quinoline can be modify to give drug Oxolinic
acid having actions similar to Nalidixic acid.
 4) Presence of -COOH group at C – 3 is essential for gyrase binding and
bacterial transport.
5) Modification of -COOH group affects activity.
6) Introduction of fluorine at C-6 and piprazine ring at C – 7 gives highly potent
drugs.
Example :- Ciprofloxacin and Norfloxacin

7) Substitution at C-7 and C-8 controls potency and pharmacokinetic of the

drug.
8) Addition of Fluorine at C-6 and C-8 gives Sparfloxacin , which has broad
spectrum of activity
Q. 13 ) Explain In Detail About Urinary tract anti-infective Agents
Ans:-
I) Urinary tract Anti-infective Agent
• The drugs which are use in treatment of urinary tract infections such drugs are
known as urinary tract anti-infective Agent
II) Symptoms
• Pain in pelvic area
• Red or pink coloured urine
• Burning sensation during urination
• Strong and continuous urge to urinate
III) Classification of Urinary tract anti-infective Agent

IV) Ciprofloxacin
A) properties
• Faint to light yellow crystalline powder
• Slightly soluble in water and dil. HCL
• practically insoluble in Ethanol
• metabolized in liver
• Store in air tight container
• protected from. Light
B) Mechanism Of Action
• inhibit enzymes Topoisomerase II And Topoisomerase IV
• Inhibit DNA gyrase
• inhibit DNA Replication, transcription process
C) Uses
• Use in treatment of Urinary tract infection
• Use in treatment of
- Pneumonia
- skin infections
- Meningitis
Q. 14 ) Explain In Detail About Anti-viral agent
Ans:-
I) Anti-viral agent
• The drugs which are use to treat viral infections such drugs are known as anti-
viral agents
• most of the anti-viral agent use for specific viral infections
• anti-viral agent inhibit development of target pathogens
II) Classification of Anti-viral agent

III) Acyclovir
A) Properties
• White or almost white crystalline powder
• soluble in dil. HCL
• slightly soluble in water
• insoluble in alcohol
• Rapidly and completely absorbed from GIT
• Metabolized in liver
• Store in air tight container • protect From light
B) Mechanism of Action

C) Uses
• Use in treatment of herpes simplex virus infection
• use in treatment of varicella zoster infection
 Unit IV
Q. 15 Explain in Detail About antifungal agent
Ans:-
I) Antifungal Agent
• The drugs which are use in treatment of fungal infections such drugs are known
as antifungal agents
• They kill the fungi or inhibit their growth
• antifungal that kill fungi are called fungicidal
• antifungal that only inhibit
II) Mechanism Of Action
• There are three types of mechanism of action for antifungal agents

A) Inhibition of Cell Wall Formation

• Inhibit many steps of cell wall Synthesis in fungi
B) Cell Membrane Disruption
• Antifungal agents bind with sterol and disrupt cell membrane
• Formation of pores and make membrane leaky
• Inhibit Ergosterol Biosynthesis
C) Inhibition of Cell Division
• Affect cell division by targeting the microtubule effect in forming the
mitotic spindle
• Inhibiting DNA transcription
III) Classification of Antifungal agent

IV) Miconazole

A) Properties
• White Crystalline powder
• soluble in water
• metabolized in liver
• Store in air tight container
• protect from light
B) Mechanism of Action
• Inhibit cytochrome P-450 enzyme
• block Ergosterol formation
• inhibit cell membranes synthesis
• increase cell membranes permeability
• leaked cellular contents
• cell deaths
C) Uses
• treat candida skin infections
• treat fungal infections like jock itch, Ringworm
Q. 15 ) Explain in Detail About Antiprotozoal agent
Ans :-
I) Antiprotozoal Agent
• The drugs which are use in treatment of infections caused by protozoa such
drugs are known as Antiprotozoal agents
• Protozoa are single cell animals
II) Various Disease caused by protozoa
1) Amoebiasis
2) Malaria
3) Toxoplasmosis
4) Cyclosporiasis
III) Classification of Antiprotozoal Agent

IV) Metronidazole
A) Properties
• white to pale yellow crystalline powder
• having slightly order
• Bitter in taste
• slightly soluble in water
• metabolized in liver by oxidation, hydration
• store in air tight container
• protected from light
B) Mechanism of action

C) Uses
• use in treatment of giardiasis,
 Q. 16) Explain in Details Anthelmintic agents
Ans:-
A) Anthelmintic Agents
The drugs which are acts against infections caused by parasitic worms such drugs are
known as Anthelmintic Agent

B) Classification of Anthelmintic Agents

i) Piperazines
• Diethylcarbamazine citrate (DEC)
• Piperazine citrate
ii) Benzimidazoles
• Albendazole
• Thiabendazole
• Mebendazole
iii) Heterocyclics
• Oxamniquine
• Praziquantel
iv) Natural products
• Ivermectin
• Avermectin
v) Vinyl pyrimidines
• Pyrantel
• Oxantel
vi) Amide
• Niclosamide
vii) Nitro derivative
• Niridazole
viii) Imidazo thiazole
• Levamisole
C) Thiabendazole

1) Properties
• White or cream coloured
• Odorless
• Nonhygroscopic
• Tasteless
• Soluble in water
• Slightly soluble in alcohol

2) Mechanism of Action
• Unknown the mechanism of action Thiabendazole
• Inhibit the specific enzyme Fumarate reductase

3) Uses
• Use to control mould and other fungal Disease in fruits and vegetables
• Use to control roundworm , hookworm infections
• Treat ear infection in cats and dogs
• Also act as cheating agent
D) Mebendazole

1) Properties
• White to yellow powder
• Having pleasant taste
• Insoluble in water And ether
• Soluble in formic acid
• Poorly absorb in GIT
• Metabolize in liver

2) Mechanism of action
• Selectively inhibit synthesis of Microtubules
• Block Polymerization of tubulin dimers in intestinal cells of parasite
• Break down of cytoplasmic microtubules
• Block uptake of glucose and other nutrients
• Immobilization and death of Helminth

3) Use
• Highly effective and have broad spectrum
• Use in treatment of nematode infestation
• Use against roundworm , hookworm, Whipworm , Threadworm , pinworm
Q. 17) Explain in details about Sulphonamides
Ans:-
A) Sulphonamides
• Any member of the group of synthetic antibiotics containing sulfonamide
molecular structure is known as Sulphonamides
• These are also known as sulpha drugs
B) History
• Sulphonamides was first antimicrobial drug.
• The first Sulphonamide was “ Prontosil ” experimented in 1932 by Bayer
AG.
• The Drug was patented by klarer and Fritz Mietzsch
C) Chemistry of Sulphonamides
• Amphoteric in nature
• Act as weak organic acid
• Weakly soluble in water
• Neutral in pH
• Use in treatment of eye infections

D) SAR of Sulphonamides
Basic structure

1) Free para amino group is essential for antibacterial activity

2) Substitution in benzene ring causes loss of activity
3) SO2NH2 group is not essential
 4) More negative So2 group at N1 exhibit greater Antibacterial activity
5) Substitution made in amide NH2 at N1 variable antibacterial activity
6) Substitution of Heterocyclic aromatic components at N4 position produce
more potent sulfa drug

E) classification of Sulphonamides

1) Based on Chemical Structure:

A) Both N¹ and N ^ 4 substituted sulfonamides :-

• Succinyl sulfathiazole
• Phthalyl sulfathiazole
B) N¹ substituted sulfonamides :-
• Sulfapyridine
• Sulfadimidine
• Sulfathiazole
• Sulfaphenazole

2) Based on duration of action

A) Long Acting :-
• Sulfamethazine
• Sulfamerazine
B) Short Acting :-
• Sulfathiazole
• Sulfasomidine
F) Sulphamethizole

1) Properties
• White, colourless crystalline solid
• Slightly soluble in hot water
• Melting point is 208° C
• Rapidly absorb in GIT
• Metabolized in liver
• Store in air tight container
• Protected from light

2) Mechanism of Action
• Competitive inhibitor of bacterial enzyme dihydropteroate Synthetase
• Prevent binding of PABA
• Inhibit Folic acid synthesis

3) Use
• Use in treatment of UTI
• Effective against most of the gram negative bacteria
G) Sulfisoxazole

1) Properties
• Odorless white to yellow crystalline powder
• Slightly bitter taste
• Melting point 191°C
• Soluble in alcohol
• It is a prodrug
• Store in air tight container
• Protected from light

2) Mechanism of Action
• Competitive inhibitor of bacterial enzyme dihydropteroate Synthetase
• Prevent binding of PABA
• Inhibit Folic acid synthesis

3) Use
• It is Antibacterial antibiotics
• Active against most gram positive and gram negative bacteria
• Treat Acute Otitis Media
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