Design and synthesis of aminothiazole-benzazole based amide: antiproliferative, antimigration activity and molecular docking studies

In this study, we synthesized a series of amide-functionalized aminothiazole-benzazole analogs for potential application in cancer treatment. The chemical structures of these compounds were confirmed using proton nuclear magnetic resonance (¹H NMR), carbon-13 nuclear magnetic resonance (¹³C NMR) spectroscopy, and high-resolution mass spectrometry (HRMS). We evaluated the cytotoxicity of these compounds against breast cancer cells (MCF-7) and lung adenocarcinoma cells (A549). Notably, Compound 6b demonstrated significant cytotoxicity, with IC₅₀ values of 17.2 ± 1.9 μM for MCF-7 cells and 19.0 ± 3.2 μM for A549 cells. Furthermore, we assessed the antimigration properties of all synthesized compounds, observing promising antiproliferative effects in both MCF-7 and A549 cells. Compound 6b exhibited a significant antimigration effect, achieving a 50.2 ± 4.7% wound healing rate in MCF-7 cells. In addition, we examined the impact of these compounds on key apoptotic proteins, including Caspase-7, PARP-1, BAX, and Bcl-2, which are critical in the regulation of programmed cell death. The binding potentials of the active compounds to BAX and Bcl-2 were also supported by docking. Results that consolidate the in vitro study were obtained from the in silico analysis. Our results suggest that these amide-functionalized aminothiazole-benzazole analogs exhibit potential as anticancer agents and merit further investigation to elucidate their mechanisms of action and therapeutic potential.