Microscale Synthesis, Characterization, and Anticancer Evaluation of Some ((E)-N-((۲-(۴-(۱H-Imidazol-۱-yl) Phenyl)-۱H-Indol-۳-yl) Methylene) Pyridin-۲-Amine Derivatives

In this study, we synthesized, characterized, and evaluated the anti-cancer potential of a novel series of ((E)-N-((۲-(۴-(۱H-imidazol-۱-yl) phenyl)-۱H-indol-۳-yl) methylene) pyridin-۲-amine derivatives. Ten derivatives (MDT-۳۲, MDT-۳۹, MDT-۴۳, MDT-۴۴, MDT-۴۵, MDT-۴۷, MDT-۵۴, MDT-۵۸, MDT-۵۹, and MDT-۶۰) were synthesized and evaluated for cytotoxicity against ER-α-positive breast cancer (T۴۷D and MCF-۷), ER-α-negative breast cancer (MDA-MB-۲۳۱), kidney (HEK-۲۹۳), and lung (A-۵۴۹) cells using the MTT assay. Tamoxifen served as the positive control. Among the tested compounds, MDT-۳۲, MDT-۴۷, MDT-۴۳, and MDT-۵۸ exhibited >۵۰% inhibition in T۴۷D cells, with MDT-۳۲, MDT-۴۷, and MDT-۴۳ showing superior activity in MCF-۷ cells compared with tamoxifen. Notably, MDT-۳۲ displayed >۵۰% inhibition of MDA-MB-۲۳۱ cells, whereas none of the compounds were cytotoxic to A-۵۴۹ cells. The presence of electron-withdrawing groups, such as fluorine, on the indole moiety (MDT-۳۲ and MDT-۴۷) enhanced anticancer activity, particularly in ER-α-positive breast cancer cells. In a competitive binding assay, MDT-۳۲ (۳۹.۱۷ ± ۱.۱۶ nM) and MDT-۴۷ (۴۱.۱۸ ± ۱.۱۸ nM) demonstrated superior binding affinities compared to tamoxifen (۴۰.۷۱ ± ۱.۴۱ nM). These results highlight the potential of MDT-۳۲ and MDT-۴۷ 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.

کلیدواژه ها:

Indole derivatives ، Anticancer ، SERD ، Cell lines ، Enzyme assay