microscale synthesis, characterization, and anticancer evaluation of some ((e)-n-((2-(4-(1h-imidazol-1-yl) phenyl)-1h-indol-3-yl) methylene) pyridin-2-amine derivatives

In this study, we synthesized, characterized, and evaluated the anti-cancer potential of a novel series of ((e)-n-((2-(4-(1h-imidazol-1-yl) phenyl)-1h-indol-3-yl) methylene) pyridin-2-amine derivatives. ten derivatives (mdt-32, mdt-39, mdt-43, mdt-44, mdt-45, mdt-47, mdt-54, mdt-58, mdt-59, and mdt-60) were synthesized and evaluated for cytotoxicity against er-α-positive breast cancer (t47d and mcf-7), er-α-negative breast cancer (mda-mb-231), kidney (hek-293), and lung (a-549) cells using the mtt assay. tamoxifen served as the positive control. among the tested compounds, mdt-32, mdt-47, mdt-43, and mdt-58 exhibited >50% inhibition in t47d cells, with mdt-32, mdt-47, and mdt-43 showing superior activity in mcf-7 cells compared with tamoxifen. notably, mdt-32 displayed >50% inhibition of mda-mb-231 cells, whereas none of the compounds were cytotoxic to a-549 cells. the presence of electron-withdrawing groups, such as fluorine, on the indole moiety (mdt-32 and mdt-47) enhanced anticancer activity, particularly in er-α-positive breast cancer cells. in a competitive binding assay, mdt-32 (39.17 ± 1.16 nm) and mdt-47 (41.18 ± 1.18 nm) demonstrated superior binding affinities compared to tamoxifen (40.71 ± 1.41 nm). these results highlight the potential of mdt-32 and mdt-47 as promising candidates for anticancer development. future studies will focus on exploring detailed mechanism-of-action, in vivo efficacy, and pharmacokinetic profiles to advance these derivatives toward clinical development.