Chemistry Department, Faculty of Science, Mansoura University, 25 El Gomhouria St, Mansoura, Dakahlia Governorate, 35516, Egypt.
Mol Divers. 2021 Feb;25(1):435-459. doi: 10.1007/s11030-020-10138-7. Epub 2020 Sep 25.
Possible application of incorporating a well-known drug (benzocaine) with cyanoacetamide function to get a powerful synthon ethyl 4-cyanoacetamido benzoate. This synthetic intermediate was used as a precursor for the synthesis of triazine, pyridone, thiazolidinone, thiazole and thiophene scaffolds containing the benzocaine core. Facile coupling, Michael addition, condensation and nucleophilic attack reactions were used to synthesize our targets. The structural features of the synthesized scaffolds were characterized using IR, H NMR, C NMR and mass spectroscopy. The antibacterial activities against Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) were evaluated using ampicillin as a reference drug. DNA/methyl-green colorimetric assay of the DNA-binding compounds was also performed. Theoretical studies of the newly synthesized compounds based on molecular docking and QSAR study were conducted. The molecular docking studies were screened by MOE software for the more potent antibacterial agent 28b and each native ligand against four of S. aureus proteins 1jij, 2xct, 2w9s and 3t07.
将一种知名药物（苯佐卡因）与氰基乙酰胺功能结合，以获得一种强大的合成物乙基 4-氰基乙酰胺苯甲酸酯。该合成中间体被用作合成三嗪、吡啶酮、噻唑烷酮、噻唑和噻吩骨架的前体，这些骨架含有苯佐卡因核心。通过易偶联、迈克尔加成、缩合和亲核攻击反应来合成我们的目标。使用红外光谱（IR）、核磁共振氢谱（1H NMR）、核磁共振碳谱（13C NMR）和质谱（MS）对合成的支架的结构特征进行了表征。使用氨苄西林作为参考药物，评估了这些支架对革兰氏阳性（金黄色葡萄球菌、枯草芽孢杆菌）和革兰氏阴性菌（大肠杆菌、铜绿假单胞菌）的抗菌活性。还对与 DNA 结合的化合物进行了 DNA/甲基-绿比色法测定。基于分子对接和 QSAR 研究对新合成的化合物进行了理论研究。使用 MOE 软件对更有效的抗菌剂 28b 和每个天然配体对 4 种金黄色葡萄球菌蛋白 1jij、2xct、2w9s 和 3t07 进行了分子对接研究筛选。
