Structure-Based Design and Virtual Screening of Indole Scaffolds Targeting Plasmodium falciparum

Abstract

The library consists of indole based thirty-five compounds were designed and screened on MAIP (MAlarial inhibitor prediction) to discover active compounds. The novel series of N-[3,5-is(trifluoromethyl)-phenyl]-3-(1-[3-(phenylamino)-3-oxopropyl]-1H-indol-3-yl}-2-cyanoacrylamide derivatives was synthesized starting from indole-3-carbaldehyde. These synthesized compounds were characterized by various spectroscopic methods in particular with FT-IR, 1H NMR and mass spectroscopy techniques. The molecules were assayed for in vitro antimalarial activity opposed to Plasmodium falciparum parasite. The tested compounds showed moderate to good antimalarial activity. To find out more specific target way to disrupt the parasite lifecycle the molecular docking was performed against PfDHFR enzyme. All the molecules result lower binding affinity than standard drug chloroquine. The highest active compound found to be (Z)-N-[3,5-bis(trifluoromethyl)phenyl]-2-cyano-3-(1-{3-[(2,6-dimethylphenyl)amino]-3-oxopropyl}-1H-indol-3-yl)acrylamide which shows –11.1 binding energy.