Synthesis and Evaluation of Substituted Pyrazoles: Potential Antimalarials Targeting the Enoyl‐ACP Reductase of Plasmodium Falciparum

Abstract

A series of 1,5‐ and 1,3‐diarylsubstituted pyrazoles were designed, synthesized, and evaluated for their ability to inhibit enoyl‐ACP reductase of Plasmodium falciparum. The inhibitory activity of these synthesized compounds was evaluated in a continuous spectrophotometric assay. Of all the compounds analyzed, NAS‐81 and NAS‐39 inhibited the enzyme with IC₅₀ values of 30 µM and 50 µM, respectively. The mode of ligand binding was investigated by docking the synthetic inhibitors at the active site of the crystal structure of the enzyme.

Keywords:

• Antimalarials
• fatty acid synthesis
• inhibitor
• substituted pyrazole

Acknowledgments

This work was supported by a grant from the Department of Biotechnology, Government of India, to N. S. and partially supported by grants from Shantha Biotechniques Pvt. Ltd., Hyderabad, to N. S. and A. S. S. K. is thankful to the Department of Biotechnology PDF program for a postdoctoral fellowship.