Synthesis, Characterization, and In Vitro and In Silico Studies of Substituted‐Vanillin Hydrazones of Anthranilic Acid and Their Quinazolin‐4(3H)‐One Analogues as Anti Breast Cancer Agents

OpenAlex İngilizce

Abstract This study synthesized a total of 18 new anthranilic acid hydrazones and quinazolin‐4( 3H )‐one derivatives, evaluating their cytotoxicity against the MCF7 and HUVEC cell lines. The anticancer effects of these compounds and their interactions with estrogen receptor alpha (ERα) and HER2 through molecular docking and molecular dynamics simulations. Cytotoxicity assays revealed that most compounds exhibited higher selectivity for MCF7 cells compared to HUVEC cells, with compounds 12, 13, 14, 23, and 29 showing superior efficacy over the standard drug 5‐fluorouracil (5‐FU). Notably, compound 12 displayed the highest selectivity index (SI = 3.9) and an IC 50 of 77.3 µM against MCF7 cells. Compounds 14 and 29 also demonstrated significant selectivity indices of 3.0 and 3.5, respectively, with IC 50 values of 111.4 µM and 74.0 µM against MCF7 cells. Molecular docking studies identified compounds 14 and 29 as strong inhibitors of ERα and HER2, with stable interactions and favorable binding profiles in docking and MD analyses. Furthermore, ADME analysis indicated good drug like properties for most compounds, aligning with Lipinski's rule of five, supporting their potential as orally bioavailable drugs. This research highlights compounds 14 , and 29 as promising candidates for targeted breast cancer therapy via inhibition of ERα and HER2