A library of pyrazole-thiazolidinone conjugates was synthesized using a molecular hybridization approach through a Vilsmeier-Haack reaction. The compounds were tested for anti-microbial activity against two Gram-positive bacteria (Staphylococcus aureus and methicillin-resistant Staphylococcus aureus) and four Gram-negative bacteria (Escherichia coli, Salmonella typhimurium, Klebsiella pneumonia and Pseudomonas aeruginosa). Among the compounds tested, 3-((2,4-dichlorophenyl)-1-(2,4-dinitrophenyl)-1H-pyrazol-yl)methylene)hydrazinecarbothioamide (3a) and 2-((3-(2-chlorophenyl)-1-(2,4 dinitrophenyl)-1H-pyrazol-4-yl)methyleneamino)thiazolidin-4-one (4b) emerged as the most potent anti-microbial compounds with minimum bactericidal concentrations of < 0.2 µM against MRSA and S. aureus. Structure-activity relationship analysis further revealed that the presence of 2,4-dichloro moiety surprisingly influenced the activity of the compounds. Molecular docking studies of the compounds into the crystal structure of topoisomerase II and topoisomerase IV suggest that compounds 3a and 4b preferably interact with the targets through hydrogen bonding.

中文翻译：

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吡唑-缩氨基硫脲及其吡唑-噻唑烷酮偶联物的抗菌评价和分子对接研究。

使用分子杂交方法通过 Vilsmeier-Haack 反应合成了吡唑-噻唑烷酮缀合物文库。测试了这些化合物对两种革兰氏阳性菌（金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌）和四种革兰氏阴性菌（大肠杆菌、鼠伤寒沙门氏菌、肺炎克雷伯菌和铜绿假单胞菌）的抗菌活性。在测试的化合物中，3-((2,4-二氯苯基)-1-(2,4-二硝基苯基)-1H-吡唑-基)亚甲基)肼碳硫酰胺(3a)和2-((3-(2-氯苯基) -1-(2,4 dinitrophenyl)-1H-pyrazol-4-yl)methyleneamino)thiazolidin-4-one (4b) 成为最有效的抗微生物化合物，对 MRSA 和 S 的最低杀菌浓度小于 0.2 µM。金黄色葡萄球菌。构效关系分析进一步表明，2,4-二氯部分的存在令人惊讶地影响了化合物的活性。化合物在拓扑异构酶 II 和拓扑异构酶 IV 的晶体结构中的分子对接研究表明，化合物 3a 和 4b 优选通过氢键与靶标相互作用。