Abstract

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, ¹H NMR, ¹³C 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.

Graphic abstract

中文翻译：

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苯佐卡因衍生物的合成、表征、抗菌评价、2D-QSAR 建模和分子对接研究。

摘要

结合具有氰基乙酰胺功能的众所周知的药物（苯佐卡因）来获得强大的合成 4-氰基乙酰胺苯甲酸乙酯的可能应用。该合成中间体用作合成含有苯佐卡因核心的三嗪、吡啶酮、噻唑烷酮、噻唑和噻吩支架的前体。使用简便的偶联、迈克尔加成、缩合和亲核攻击反应来合成我们的目标。合成支架的结构特征使用 IR、¹ H NMR、¹³ C NMR 和质谱进行表征。对革兰氏阳性菌（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) 使用氨苄青霉素作为参考药物进行评估。还对 DNA 结合化合物进行了 DNA/甲基绿比色分析。对新合成的化合物进行了基于分子对接和QSAR研究的理论研究。分子对接研究通过 MOE 软件筛选出更有效的抗菌剂28b和针对金黄色葡萄球菌蛋白 1jij、2xct、2w9s 和 3t07中四种的每种天然配体。

图形摘要