Scribd
Upload
12 views

Bioisosterism

Bioisosterism is a concept in medicinal chemistry that involves replacing molecular fragments to optimize drug properties while maintaining biological activity. Bioisosteres are classified into classical and non-classical categories, with the aim of enhancing pharmacological effects and reducing toxicity. Examples include modifications in drugs like 5-Fluorouracil and case studies on sulfonamides, Zidovudine, and fluoroquinolones demonstrating the effectiveness of bioisosteric replacements in drug design.

Uploaded by

Bhujithra Mohanavel
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
12 views

Bioisosterism

Bioisosterism is a concept in medicinal chemistry that involves replacing molecular fragments to optimize drug properties while maintaining biological activity. Bioisosteres are classified into classical and non-classical categories, with the aim of enhancing pharmacological effects and reducing toxicity. Examples include modifications in drugs like 5-Fluorouracil and case studies on sulfonamides, Zidovudine, and fluoroquinolones demonstrating the effectiveness of bioisosteric replacements in drug design.

Uploaded by

Bhujithra Mohanavel
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
You are on page 1/ 3

1. What is Bioisosterism in Analog-Based Drug Design?

Bioisosterism is a key concept in medicinal chemistry that involves the replacement of one molecular
fragment with another that has similar chemical and physical properties while retaining or improving
biological activity. This concept is used to optimize the pharmacokinetic profile, increase selectivity,
reduce toxicity, and improve metabolic stability of drug molecules. Bioisosteric modifications help in
scaffold hopping, enzyme inhibition, and the development of novel drug candidates.

2. How are Bioisosteres Classified in Drug Design?

Bioisosteres are classified into two main categories: classical and non-classical bioisosteres.

• Classical bioisosteres follow the Grimm’s hydride displacement law and include monovalent
(-NH₂, -CH₃, -OH), bivalent (-CH₂-, -NH-, -O-), trivalent (-CH=, -N=), and tetravalent (C, Si)
substitutions.

• Non-classical bioisosteres do not follow traditional rules but mimic the molecular shape and
function, including replacements such as carbonyl groups, amides, carboxylic acids, esters,
and ring equivalents.
•

3. What is the Purpose of Bioisosteric Replacement in Drug Development?

The primary goal of bioisosteric replacement is to enhance the pharmacological and therapeutic
properties of a drug while minimizing adverse effects. It helps in:

• Improving metabolic stability


• Enhancing receptor binding affinity

• Reducing toxicity

• Modifying drug solubility and bioavailability

• Preventing unwanted metabolic transformations

4. Example of a Drug Modified Using Bioisosteric Replacement

A well-known example is 5-Fluorouracil (5-FU), an anticancer drug where the hydrogen atom in uracil
is replaced with fluorine. This modification enhances its ability to inhibit thymidylate synthase, an
enzyme crucial for DNA replication in cancer cells.

5. Three Case Studies of Bioisosteric Replacement in Drug Design

Case Study 1: Sulfonamides as Antibacterial Agents

Prontosil, an early antibacterial drug, was discovered to be a prodrug that metabolizes into
sulfanilamide. The sulfonamide (-SO₂NH₂) group in sulfanilamide acts as a bioisosteric replacement
for the carboxyl (-COOH) group in para-aminobenzoic acid (PABA), allowing the drug to competitively
inhibit bacterial folate synthesis.

Case Study 2: Antiviral Drug Zidovudine (AZT)

Zidovudine, an anti-HIV drug, was developed through the bioisosteric replacement of the hydroxyl (-
OH) group in thymidine with an azido (-N₃) group. This modification prevents the incorporation of
the drug into viral DNA, thereby inhibiting reverse transcriptase and viral replication.

Case Study 3: Fluoroquinolones as Antibacterial Agents

The introduction of a fluorine (-F) atom at the 6th position of quinolone antibiotics led to the
development of fluoroquinolones, such as ciprofloxacin. This bioisosteric modification enhanced
bacterial enzyme affinity, broadened the antibacterial spectrum, and improved drug potency.

These case studies highlight the significance of bioisosteric modifications in improving drug efficacy
and safety in medicinal chemistry.

You might also like