Synthesis of fusidic acid bioisosteres as antiplasmodial agents and molecular docking studies in the binding site of elongation factor-G

Abstract

A series of fusidic acid derivatives was synthesized by replacing the carboxylic acid group with various bioisosteres and evaluated in vitro against the chloroquine-sensitive NF54 strain of malaria parasite Plasmodium falciparum. Most of these derivatives showed a 2–35 fold increase in activity as compared to fusidic acid and had a good selectivity index. Further, docking experiments of fusidic acid and the most active derivative 18 within the active site of plasmodial elongation factor-Gs suggested that the binding orientation of 18 is similar to fusidic acid, but with slightly better docking score.