Synthesis, computational, and biological evaluation of novel indolophenyl carboxamides as potential antimalarial...

This study involves the synthesis of indolophenyl carboxamides, computational analysis, and assessing the compounds against Plasmodium falciparum strains.

Indolophenyl carboxamides were synthesized and characterized using ¹H NMR and ¹³C NMR, and HRMS techniques, and were evaluated against the P. falciparum 3D7 and C580Y strains by using the SYBR Green I assay.

Compounds 1, 7, 8, and 9 showed potent antimalarial activity against Pf3D7 and Pf C580Y with IC₅₀ values of 8.9 and 3.4 µM, 5.5 and 2.2 µM, 10.1 and 14.0 µM, and 12.2 and 28.6 µM, respectively, and were nontoxic to human cells. Further, in silico studies confirmed Plasmodium dihydrofolate reductase as the target of indolophenyl carboxamides. This study identifies indolophenyl carboxamides, including bisindole, as promising new antimalarial agents effective against sensitive and drug-resistant P. falciparum.