Synthesis, computational, and biological evaluation of novel indolophenyl carboxamides as potential antimalarial agents
Priya Mondal, Asha Kiran Tudu, Nishtha Tiwari, Tanish, Rahul Kewal Kumar, Priyanka Rani, Supriya Sharma, Kapil Vashisht, Kailash Chand Pandey, Gautam Kumar · Future Medicinal Chemistry · 2025
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 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.Results and conclusion 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.