فهرست نشریات علمی دسترسی آزاد ایران

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.