A 15-year-old girl with falciparum malaria fails chloroquine therapy. Artemisinin combination therapy (ACT) is started. The primary mechanism of artemisinins involves:

• A Inhibition of dihydropteroate synthetase, blocking folate synthesis in the parasite
• B Inhibition of mitochondrial cytochrome bc1 complex in Plasmodium
• C Covalent alkylation of hemozoin crystal surfaces, preventing further heme sequestration
• D Heme-catalyzed cleavage of the endoperoxide bridge generating free radicals ✓

Explanation

Artemisinins contain a unique 1,2,4-trioxane (endoperoxide) bridge that is cleaved by heme-derived iron (released during hemoglobin digestion by the parasite), generating highly reactive carbon-centered free radicals. These radicals alkylate and damage parasite proteins (particularly PfATP6, the SERCA pump) and membranes. The selective toxicity depends on the parasite's high intracellular heme concentration. Artemisinins act very rapidly on all asexual stages and early gametocytes. Atovaquone-proguanil inhibits cytochrome bc1; sulfa drugs inhibit dihydropteroate synthetase.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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