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Bioorg Med Chem Lett. 2014 Jan 1;24(1):90-5. doi: 10.1016/j.bmcl.2013.11.079. Epub 2013 Dec 4.

Design, synthesis and antibacterial activities of 5-(pyrazin-2-yl)-4H-1,2,4-triazole-3-thiol derivatives containing Schiff base formation as FabH inhibitory.

Author information

1
Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
2
Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: botanyzh@163.com.
3
Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: zhuhl@nju.edu.cn.

Abstract

A series of novel schiff base derivatives (H(1)-H(20)) containing pyrazine and triazole moiety have been designed and synthesized, and their biological activities were also evaluated as potential inhibitors of β-ketoacyl-acyl carrier protein synthase III (FabH). These compounds were assayed for antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis and Bacillus amyloliquefaciens and selected compounds among them were tested for their Escherichia coli FabH inhibitory activity. Based on the biological data, compound H(17) showed the most potent antibacterial activity with MIC values of 0.39-1.56μg/mL against the tested bacterial strains and exhibited the most potent E. coli FabH inhibitory activity with IC50 of 5.2μM, being better than the positive control Kanamycin B with IC50 of 6.3μM. Furthermore, docking simulation was performed to position compound H(17) into the E. coli FabH active site to determine the probable binding conformation. This study indicated that compound H(17) has demonstrated significant E. coli FabH inhibitory activity as a potential antibacterial agent and provides valuable information for the design of E. coli FabH inhibitors.

KEYWORDS:

1,2,4-Triazole; Antibacterial; FabH inhibitor; Schiff base; Structure–activity relationship

PMID:
24332628
DOI:
10.1016/j.bmcl.2013.11.079
[Indexed for MEDLINE]

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