Synthesis and Bioevaluation of Substituted 2,11-dihydroimidazo[1′,5′:1,2]pyrido-[3,4-b]indoles as antiplasmodial and antiproliferative agents

Abstract

The synthesis and bioevaluation of a new series of substituted 2,11-dihydroimidazo[1’,5’:1,2]pyrido-[3.4-b]indoles as antiplasmodial and antiproliferative agents are described. Several compounds (16aaf, 16abf, 16acf, 16adq, 16aeo, and 16afe ) exhibited significant antiplasmodial activity againist both chloroquine-sensitive (3D7) and resistant (K1) strains of Plasmodium falciparum. Mechanistic studies indicated that these compounds induced DNA and mitochondrial damage, leading to parasite growth arrest with no recovery even after drug pressure removal. In antiproliferative assays, compounds 16abq and 16aeb were the most potent analogues showing inhibitory activity against triple-negative breast cancer (TNBC) cells while displaying comparatively low cytotoxicity toward non-tumorigenic cells, suggesting a favorable selectivity profile.