2,4‐Bis(2‐(E)‐arylidenehydrazinyl)quinazolines: Expeditious Synthesis, Characterization, Antiproliferative Effects against Breast Cancer Cell Line and Molecular Docking Studies

Considering the immense significance of molecular hybridization in development of efficacious antiproliferative agents, the present research work demonstrates the expeditious synthesis of twelve electronically different and novel 2,4‐bis(2‐(E)‐arylidenehydrazinyl)quinazolines 4 a–4 l. Their exact molecular structures have been established by careful analysis of spectroscopic (IR, 1H & 13C‐NMR) and HRMS data. Observed results from the MTT assay indicated that all synthesized derivatives 4 a–4 l displayed substantial growth arrest for breast (MCF‐7) cancer cell line. Specifically, 2,4‐bis(2‐(E)‐4‐methoxy benzylidenehydrazinyl)quinazoline (4 a) and 2,4‐bis(2‐(E)‐4‐bromobenzylidenehydrazinyl) quinazoline (4 b) displayed lowest GI50=139.34±7.44 μM and 145.34±2.11 μM respectively, against breast (MCF‐7) cancer cell line. Additionally, molecular docking studies have been performed to investigate the type of favourable interactions of quinazoline bis‐hydrazones with active sites of protein (PDB ID : 4ASD). Computational studies show that derivative 4 a displayed high binding affinity into the ATP binding sites of 4ASD, which support in vitro results obtained in the present study. The present study demonstrates the expeditious synthesis of some novel 2,4‐bis(2‐(E)‐arylidenehydrazinyl)quinazolines under mild reaction conditions and thorough spectroscopic (IR, 1H & 13C‐NMR) and HRMS characterization. Amongst of them, especially 2,4‐bis‐ (2‐(E)‐4‐methoxybenzylidenehydrazinyl)quinazoline (4 a) displayed lowest GI50=139.34±7.44 μM value among all against MCF‐7 (breast) cancer cell line and also shows highest binding affinity into the ATP binding sites of 4ASD.