2, 4‐Bis(2‐(E)‐arylidenehydrazinyl)quinazolines: Expeditious Synthesis, Characterization, Antiproliferative Effects against Breast Cancer Cell Line and Molecular Docking Studies. Issue 38 (10th October 2022) - Kumar, Ravinder
Abstract: 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, 1 H & 13 C‐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. Abstract : 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, 1 H & 13 C‐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.