Exploration of the cytotoxic and microtubule disruption potential of novel imidazo[1,5-a]pyridine-based chalcones†

Abstract

In continuation of our efforts to develop new anticancer compounds, a new series of imidazo[1,5-a]pyridine-chalcone derivatives was designed, synthesized, characterized, and evaluated for its cytotoxicity against five human cancer cell lines, i.e., breast (MDA-MB-231), colon (RKO), bone (Mg-63), prostate (PC-3), and liver (HepG2) cell lines, as well as a normal cell line (HEK). Among the synthesized compounds, two exhibited promising cytotoxicity against the MDA-MB-231 cell line with IC₅₀ values of 4.23 ± 0.25 μM and 3.26 ± 0.56 μM. We also studied apoptotic induction of the compounds using annexin V-FITC/PI staining, and ROS-mediated mitochondrial damage was elucidated using DCFDA, followed by JC-1 staining. The potential activity of the compounds was further confirmed by immuno-fluorescence and molecular docking studies, which revealed the anticancer activity of active compounds through binding and microtubule disruption.