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标题：Synthesis, in Vitro and in Silico Studies of Some Novel 5-Nitrofuran-2-yl Hydrazones as Antimicrobial and Antitubercular Agents
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作者：Hatem Abdel-Kader Abdel-Aziz ; Wagdy Mohamed Eldehna ; Mohamed Fares 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2015
卷号：38
期号：10
页码：1617-1630
DOI：10.1248/bpb.b15-00439
出版社：The Pharmaceutical Society of Japan
摘要：In this study, we synthesized two series of novel 5-nitrofuran-2-carbohydrazides 21a – h and 22a – e in addition to a third series of thiophene-2-carbohydrazides 23a – g to develop potent antimicrobial and/or antitubercular agents. The newly synthesized compounds were evaluated in vitro for their antimicrobial and antimycobacterial activities. Most of the 5-nitrofuran-2-carbohydrazides 21a – h and 22a – e displayed variable activity against Aspergillus fumigates , Staphylococcus aureus, Streptococcus pneumonia, Bacillis subtilis , Salmonella typhimurium , Klebsiella pneumonia , Escherichia coli and Mycobacterium tuberculosis . The sulfonamide derivative 21f exhibited superior potency and broad-spectrum antimicrobial activity with minimum inhibitory concentration (MIC)=0.06–0.98 µg/mL and antimycobacterial activity with MIC=3.9 µg/mL. The 5-nitrofuran-2-carbohydrazides 21a , b , g , h and 22a – c exhibited significant antibacterial activity with MIC values in the range of 0.12–7.81 µg/mL. The significances of the 5-nitrofuran moiety and sulfonamide function were explored via the structure–activity relationship (SAR) study. In addition, docking studies revealed that the p -amino benzoic acid (PABA) and binding pockets of the dihydropteroate synthase (DHPS) were successfully occupied by compound 21f . Furthermore, two quantitative structure–activity relationship (QSAR) models were built to explore the structural requirements which controlled the activity.