Design, synthesis and biological evaluation of novel 2-methylpyrimidine-4-ylamine derivatives as inhibitors of Escherichia coli pyruvate dehydrogenase complex E1
Design, synthesis and biological evaluation of novel 2-methylpyrimidine-4-ylamine derivatives as inhibitors of Escherichia coli pyruvate dehydrogenase complex E1
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新型2-甲基嘧啶-4-基胺衍生物作为大肠杆菌丙酮酸脱氢酶复合物E1抑制剂的设计、合成和生物学评价
DOI：
10.1016/j.bmc.2012.01.019
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发表时间：
2012-03-01
影响因子：
3.5
通讯作者：
He, Hongwu
中科院分区：
文献类型：
--
作者：
He, Junbo;Feng, Lingling;He, Hongwu
As potential inhibitors of Escherichia coli pyruvate dehydrogenase complex E1 (PDHc E1), a series of novel 2-methylpyrimidine-4-ylamine derivatives were designed based on the structure of the active site of PDHc E1 and synthesized using 'click chemistry'. Their inhibitory activity in vitro against PDHc E1 and fungicidal activity were examined. Some of these compounds such as 3g, 3l, 3n, 3o, and 5b demonstrated to be effective inhibitors of PDHc E1 from E. coli and exhibited antifungal activity. SAR analysis indicated that both, the inhibitory potency against E. coli PDHc E1 and the antifungal activity of title compounds, could be increased greatly by optimizing substituent groups in the compounds. The structures of substituent group in 5-position on the 1,2,3-triazole and 4-position on the benzene ring in title compounds were found to play a pivotal role in both above-mentioned biological activities. Amongst all the compounds, compound 5b with iodine in the 5-position of 1,2,3-triazole and with nitryl group in the 4-position of benzene ring acted as the best inhibitor against PDHc E1 from E. coli. It was also found to be the most effective compound with higher antifungal activity against Rhizoctonia solani and Botrytis cinerea at the dosage of 100 mu g mL(-1). Therefore, in this study, compound 5b was used as a lead compound for further optimization. (C) 2012 Elsevier Ltd. All rights reserved.
