New 2H‐Chromene‐Based Hydrazone Derivatives as Promising Anti‐Breast Cancer Agents: Efficient Synthesis, Spectral Characterization, Molecular Docking, and ADMET Studies

A new series of 2 H ‐chromene‐based hydrazones ( 10 a – w , 12 a – d , and 14 a – d ) were efficiently synthesized by the reaction of substituted 2 H ‐chromene aldehydes ( 8 a – w ) with various hydrazines ( 9 , 11 , and 13 ) in absolute ethanol under microwave irradiation as well as by lemon juice mediated conventional heating. The structures of synthesized target molecules were identified by spectroscopic analysis methods ( 1 H NMR, 13 C NMR, FT‐IR, and HRMS). The in vitro anticancer activity of the new 2 H ‐chromene‐based hydrazones were evaluated on the three breast cancer cell lines (MCF‐7, MDA MB‐231, and MDA MB‐468) by MTT assay. Among these synthesized compounds, 10 r and 12 b exhibited the most potent antiproliferative activities with IC 50 values at 9.12±0.45 μM and 10.71±0.67 μM respectively, against MCF‐7 cell. Flowcytometric analysis revealed that these two potent compounds, 10 r and 12 b arrested the cell cycle at the G2/M phase and induced apoptosis of proteins in a dose‐dependent manner. It was further confirmed by Hoechst staining and Annexin V‐FITC assay. Additionally, compounds 10 r and 12 b were examined by in silico molecular docking, which revealed that compound 10 r displayed excellent binding affinity energy of around −10 kcal/mol with human HER2 receptor. Also, the ADME studies validated the hybrid compounds showing promising physicochemical, pharmacokinetic, and drug‐like attributes. Broadly, these results underscored the potential of 2 H ‐chromene‐based hydrazone derivatives as promising anticancer agents.