Thiophene functionalised chalcones with anticancer potential: Synthesis, molecular docking, molecular dynamics, and cytotoxicity evaluation

• Six novel thiophene-functionalized chalcones were successfully synthesized and characterized. • Molecular docking and molecular dynamics simulations revealed strong binding affinities of the chalcones to CDK2 and VEGFR2 targets. • In vitro cytotoxicity assays identified two chalcones with significant, concentration-dependent anticancer activity. • Thiophene substitution enhances chalcone interactions with cancer-related targets, indicating potential as anticancer agents. • Findings support further optimization and development of thiophene-based chalcones for cancer therapy. Thiophene-substituted chalcones have shown enhanced biological activity, particularly in anticancer research. Six novel thiophene-functionalized chalcones (CHA1-CHA6) are synthesized. In silico screening assessed the compounds' drug-likeness using Lipinski’s rule of five, ADME properties, and toxicity profiles. Molecular docking studies were conducted against key protein targets CDK2 and VEGFR2 to predict binding affinities, identifying CHA1 and CHA3 as the most promising compounds. In vitro cytotoxicity was evaluated using MCF-7 breast cancer cell lines through an MTT assay, revealing that CHA1 and CHA3 exhibit concentration-dependent cytotoxicity, with IC50 values of 19.576 µM and 25.348 µM, respectively. CHA1 demonstrated more significant activity, making it a potential lead compound for further investigation. Molecular dynamics simulation shows a stable protein-ligand complex with strong binding affinity and consistent interactions, indicating the ligand’s potential for further drug development. Thiophene-substituted chalcones, particularly CHA1, show promise as an anticancer agent, and further research is encouraged to explore their therapeutic potential in cancer treatment.