Design, synthesis, anticancer evaluation and molecular docking studies of new imidazo [ 2, 1-b ] thiazole -based chalcones

A new series of imidazo[2, 1-b]thiazole-based chalcone derivatives were designed, synthesized, and tested for their anticancer activities. Firstly, the cytotoxic ability of the compounds was tested on three different types of cancer cells, namely colorectal adenocarcinoma (HT-29), lung carcinoma (A-549), breast adenocarcinoma (MCF-7), and mouse fibroblast cells (3T3-L1) by XTT tests. Afterwards, further anticancer activity studies with the compound 3j having the lowest IC 50 and highest SI values were performed on MCF-7 cells. XTT results revealed that all the test compounds exhibited much higher cytotoxic activity on the cancer cells than that of normal 3T3-L1 cells. Among the compounds, 3j especially stood out with its IC 50 (9.76 µM) and SI (14.99) values on MCF-7 cells. Flow cytometry analysis proved that 3j -treated MCF-7 cells was resulted in the mitochondrial membrane depolarization, multicaspase activation, and ultimately apoptosis. Additionally, in silico molecular docking approaches were carried out to confirm the experimental observations and investigate the efficacy of the compound 3j . The interactions of 3j on DNA dodecamer and caspase-3 were investigated by molecular docking studies. Based on these interactions, the active amino acids in the binding site were determined and their free binding energies (ΔG Bind ) were calculated.