TITLE:
Design, Synthesis and Characterization of Novel Sulfonamides Derivatives as Anticancer Agent Targeting EGFR TK, and Development of New Methods of Synthesis by Microwave Irradiation
AUTHORS:
Souad Akili, Djamila Ben Hadda, Yaser Bitar, Amir Balash, Mustapha Fawaz Chehna
KEYWORDS:
Sulfonamide, Anticancer, EGFR, TMLR, 5EDQ, Molegro Virtual Docker, Sul-famethoxazole, Sulfanilamide, Microwave
JOURNAL NAME:
International Journal of Organic Chemistry,
Vol.11 No.4,
December
8,
2021
ABSTRACT: Some novel sulfonamide-derivatives were designed to develop novel kinase
inhibitors. The molecular docking study was performed for the designed
compounds against epidermal growth factor kinase receptor T790M/L858R (TMLR)
(PDB ID: 5EDQ) to identify new drug candidates for treating cancer. Binding
free energy was calculated by Molegro virtual docker (MVD) to select the most
promising hits. The corresponding docking score values into EGFR (TMLR) of 4b
gave the best energy docking -147.213 Kcal/mol. And some of the designed
sulfonamide derivatives have been synthesized by conventional method in
addition to a microwave-assisted method of synthesis. The reaction of an amino
group-containing drug; sulfamethoxazole and sulfanilamide with carbonyl group
in benzoyl chloride and phthalic acid in basic media, generated a series of
sulfonamide derivatives. The structures of all the synthesized compounds were
well characterized by Mass spectrometry (MS), Infrared spectroscopy (IR), 1H
nuclear magnetic resonance (1H NMR), 13C nuclear magnetic
resonance (13C NMR) and elemental analysis. After obtaining
experimental data regarding the yield and the time taken for the synthesis by
both the approaches, conventional and microwave-assisted method, it was shown
that the microwave-assisted method gave higher yield with shorter time and
higher temperature compared to conventional heating methods.