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

Abstract

A new series of 2H‐chromene‐based hydrazones (10 a–w, 12 a–d, and 14 a–d) were efficiently synthesized by the reaction of substituted 2H‐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 (1H NMR, 13C NMR, FT‐IR, and HRMS). The in vitro anticancer activity of the new 2H‐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 IC50 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 2H‐chromene‐based hydrazone derivatives as promising anticancer agents.