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

新型吲哚苯基甲酰胺类化合物的合成、计算和生物学评价及其作为潜在抗疟药物的潜力

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Abstract

AIMS: This study involves the synthesis of indolophenyl carboxamides, computational analysis, and assessing the compounds against Plasmodium falciparum strains. MATERIALS AND METHODS: Indolophenyl carboxamides were synthesized and characterized using (1)H NMR and (13)C NMR, and HRMS techniques, and were evaluated against the P. falciparum 3D7 and C580Y strains by using the SYBR Green I assay. RESULTS AND CONCLUSION: Compounds 1, 7, 8, and 9 showed potent antimalarial activity against Pf3D7 and Pf C580Y with IC(50) 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.

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