Question

According to the SAR of Chloroquine electron:

• A. Withdrawing group at 6^th position of the quinoline ring is important for the inhibition of hemozoin formation
• B. Donating group at 7^th position of the quinoline ring is important for the inhibition of hemozoin formation
• C. Donating group at 6^th position of the quinoline ring is important for the inhibition of hemozoin formation
• D. Withdrawing group at 7^th position of the quinoline ring is important for the inhibition of hemozoin formation

Answer 1

The Correct Option is D

Step 1: Understanding the Question:
The question tests the structure-activity relationship rule behind chloroquine's antimalarial action.

Step 2: Key Concept:
Chloroquine works by binding to free heme released during hemoglobin digestion and preventing its polymerization into hemozoin, and how well the quinoline ring binds heme depends on the electronic character introduced by ring substituents.

Step 3: Detailed Explanation:
The 7-position of the 4-aminoquinoline ring, occupied by chlorine in chloroquine, is the critical site for activity. An electron-withdrawing group there pulls electron density away from the ring nitrogen, which strengthens the drug's ability to bind ferriprotoporphyrin IX and block hemozoin formation. Swapping this for an electron-donating group, or moving the substituent to position 6, weakens the binding and lowers antimalarial activity.

Step 4: Final Answer:
Withdrawing group at the 7th position of the quinoline ring.