Synthesis and computational study of 4-hydroxylbenzamide analogous as potential anti-breast cancer agent

Due to their role in cell growth and survival, HDAC (II), JAK 2 and EGFR receptors are important targets in many chemotherapies that aim to produce their biological response in malignancy solid tumors. In this work, several 4-hydroxybenzamide analogues coupled with 1,3benzodioxole, a,ss-unsaturated carbonyl, and tert-butyl ester bases small molecules were synthesized via imidation, EDC coupling, and etherification reactions, then bio-active 4-hydroxybenzamide analogues were studied using quantum calculations and molecular docking. The Frontier molecular orbitals and energy gap values were calculated using Time-Dependent Density Functional Theory (TD-DFT). Docking results showed A and E as potent JAK2 inhibitors. B, C, and F may be good HDAC II inhibitors. D may act as a potent EGFR inhibitor. These were followed by cytotoxic evaluation of 4-hydroxybenzamide analogues on human estrogen receptor breast cancer cells (MCF-7), metastatic breast adenocarcinome cancer cells (MDA-MB-231), and fibroblast cells (NIH/3T3) respectively. Molecule E was found to have insignificant apoptosis against MCF 7 cell line and MDM-MD-231 cell lines with IC50 value 5.0 mg/mL and 5.0 mg/mL respectively. (c) 2021 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).