Question

Methotrexate, used as an antimetabolite, is a product of N-methylation of para-aminobenzoic acid and pyridine hydroxyl. The isosteric group is

• A. SH
• B. CH_3
• C. NH_2
• D. CF_3

Hint:

Isosteres are useful in drug design for improving activity or metabolic stability by structural mimicry.

Answer 1

The Correct Option is B

- Methotrexate is a folic acid analog and acts as a competitive inhibitor of the enzyme dihydrofolate reductase (DHFR), which is essential for DNA synthesis.
- In structure-activity relationships (SAR), bioisosteric replacement is a concept where functional groups with similar physical or chemical properties are substituted without significantly altering the biological activity.
- The N-methyl group (CH\textsubscript{3}) acts as a classical isosteric group in methotrexate, mimicking structural features of naturally occurring folates to retain binding affinity and metabolic stability.
- Among the given options, CH\textsubscript{3} serves as a non-polar, small group that can mimic hydrogen or methyl moieties in bioisosterism.
- Therefore, the correct isosteric group relevant to methotrexate’s activity is CH\textsubscript{3}.