Institute of Chemical Technology, Nathalal Parikh Marg, Matunga, Mumbai 400 019, India.
Bioorg Med Chem Lett. 2010 Mar 1;20(5):1623-5. doi: 10.1016/j.bmcl.2010.01.031. Epub 2010 Jan 20.
In an attempt to identify potential new agents active against tuberculosis, 20 novel phenylacrylamide derivatives incorporating cinnamic acids and guanylhydrazones were synthesized using microwave assisted synthesis. Activity of the synthesized compounds was evaluated using resazurin microtitre plate assay (REMA) against Mycobacterium tuberculosis H37Rv. Based on empirical structure-activity relationship data it was observed that both steric and electronic parameters play major role in the activity of this series of compounds. Compound 7s (2E)-N-((-2-(3,4-dimethoxybenzylidene) hydrazinyl) (imino) methyl)-3-(4-methoxyphenyl) acrylamide showed MIC of 6.49microM along with good safety profile of >50-fold in VERO cell line. Thus, this compound could act as a potential lead for further antitubercular studies.
为了寻找可能对抗结核病的新型药物,我们采用微波辅助合成法,合成了 20 种新型苯丙烯酰胺衍生物,其中包含肉桂酸和脒基腙。我们使用 Resazurin 微量板测定法(REMA)评估了合成化合物对结核分枝杆菌 H37Rv 的活性。根据经验结构-活性关系数据,我们观察到空间和电子参数在这一系列化合物的活性中都起着重要作用。化合物 7s(2E)-N-((-2-(3,4-二甲氧基苄叉)腙基)(亚氨基)甲基)-3-(4-甲氧基苯基)丙烯酰胺的 MIC 值为 6.49µM,同时在 VERO 细胞系中的安全性超过 50 倍。因此,该化合物可能成为进一步抗结核研究的潜在先导化合物。