Synthesis and Biological Screening of Novel Indole-derived Imidazo[2,1-b][1,3,4]thiadiazoles as EGFR Targeting Anticancer Agents

A series of indole-derived imidazo[2,1-b][1,3,4]thiadiazole scaffolds were synthesized, and their structures were confirmed by H-1 and C-13 NMR spectroscopy, ESI mass spectrometry, and element analysis. The synthesized compounds were tested for their in vitro anticancer activity. Among all compounds, 2-(1H-Indol-2-yl)-6-(4-nitrophenyl)imidazo[2,1-b][1,3,4]thiadiazole exhibited the highest activity against MCF-7, A549, and Colon-205 cell lines. 6-(4-Bromophenyl)-2-(1H-indol-2-yl)imidazo[2,1-b][1,3,4]thiadiazole and 6-(4-chlorophenyl)-2-(1H-indol-2-yl)imidazo[2,1-b][1,3,4]thiadiazole displayed good activity against the tested cell lines. In silico molecular docking of the products was performed to evaluate their potential as EGFR inhibitors. 2-(1H-Indol-2-yl)-6-(4-nitrophenyl)imidazo[2,1-b][1,3,4]thiadiazole, 6-(4-bromophenyl)-2-(1H-indol-2-yl)imidazo[2,1-b][1,3,4]thiadiazole, and 6-(4-chlorophenyl)-2-(1H-indol-2-yl)imidazo[2,1-b][1,3,4]thiadiazole were predicted to have the lowest binding energies. The theoretical results correlate well with the results of in vitro biological tests.