Design, Synthesis and Characterization of Novel Sulfonamides Derivatives as Anticancer Agent Targeting EGFR TK, and Development of New Methods of Synthesis by Microwave Irradiation  

作　　者：Souad Akili Djamila Ben Hadda Yaser Bitar Amir Balash Mustapha Fawaz Chehna Souad Akili;Djamila Ben Hadda;Yaser Bitar;Amir Balash;Mustapha Fawaz Chehna(Department Quality Control and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Aleppo, Aleppo, Syria;Department Quality Control and Pharmaceutical Chemistry, Faculty of Pharmacy, Ebla Private University, Aleppo, Syria;Department of Pharmaceutical Chemistry, Institute of Pharmacy, University of Marburg, Marburg, Germany)

机构地区：[1]Department Quality Control and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Aleppo, Aleppo, Syria [2]Department Quality Control and Pharmaceutical Chemistry, Faculty of Pharmacy, Ebla Private University, Aleppo, Syria [3]Department of Pharmaceutical Chemistry, Institute of Pharmacy, University of Marburg, Marburg, Germany

出　　处：《International Journal of Organic Chemistry》2021年第4期199-223,共25页有机化学国际期刊（英文）

摘　　要：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), ^{<span style="font-family:Verdana;">1</span>}<span style="font-family:Verdana;">H nuclear magnetic resonance (</span>^{<span style="font-family:Verdana;">1</span>}<span style="font-family:Verdana;">H NMR), </span>^{<span style="font-family:Verdana;">13</span>}<span style="font-family:Verdana;">C nuclear magnetic resonance (</span>^{<span style="font-family:Verdana;">13</span>}<span style="font-family:Verdana;">C 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.</span>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), ^{<span style="font-family:Verdana;">1</span>}<span style="font-family:Verdana;">H nuclear magnetic resonance (</span>^{<span style="font-family:Verdana;">1</span>}<span style="font-family:Verdana;">H NMR), </span>^{<span style="font-family:Verdana;">13</span>}<span style="font-family:Verdana;">C nuclear magnetic resonance (</span>^{<span style="font-family:Verdana;">13</span>}<span style="font-family:Verdana;">C 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.</span>

关 键 词：SULFONAMIDE Anticancer EGFR TMLR 5EDQ Molegro Virtual Docker Sul-famethoxazole SULFANILAMIDE Microwave 

分 类 号：O62[理学—有机化学]