In this study, we synthesized a series of amide-functionalized aminothiazole-benzazole analogs for potential application in cancer treatment.The chem structures of these compounds were confirmed using proton NMR (1H NMR), carbon-13 NMR (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.That consolidate the in vitro study were obtained from the in silico anal.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.The synthesis of novel aminothiazole-benzazole-based amide derivatives as potential anticancer agents has been reported.These compounds were evaluated for their cytotoxic activity against MCF-7 and A549 cancer cell lines, exhibiting IC50 values ranging from 17.2 to 80.6 μM.Furthermore, the cytotoxic compounds demonstrated significant antimigration effects and induced apoptosis in both MCF-7 and A549 cell lines.Addnl., the results confirming the in vitro study were supported by in silico anal.