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娃儿藤生物碱的结构类似物可能不是功能类似物。

Structural analogs of tylophora alkaloids may not be functional analogs.

作者信息

Gao Wenli, Chen Annie Pei-Chun, Leung Chung-Hang, Gullen Elizabeth A, Fürstner Alois, Shi Qian, Wei Linyi, Lee Kuo-Hsiung, Cheng Yung-Chi

机构信息

Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA.

出版信息

Bioorg Med Chem Lett. 2008 Jan 15;18(2):704-9. doi: 10.1016/j.bmcl.2007.11.054. Epub 2007 Nov 21.

Abstract

Phenanthroindolizidine-based tylophora alkaloids have been reported to have potential antitumor, anti-immuno and, anti-inflammatory activity. The structure-activity relationships of a series of tylophora alkaloids were studied to guide future drug design. Our results indicate that although these compounds are structural analogs, their potency of cytotoxicity, selectivity against NF-kappaB signaling pathway, and their inhibitory effects against protein and nucleic acid synthesis are different. Because they do not have an identical spectrum of targets, the studied compounds are structural, but may not be functional analogs.

摘要

据报道,基于菲并吲哚里西啶的娃儿藤生物碱具有潜在的抗肿瘤、抗免疫和抗炎活性。研究了一系列娃儿藤生物碱的构效关系,以指导未来的药物设计。我们的结果表明,尽管这些化合物是结构类似物,但它们的细胞毒性效力、对NF-κB信号通路的选择性以及对蛋白质和核酸合成的抑制作用各不相同。由于它们没有相同的靶点谱,所研究的化合物是结构上的,但可能不是功能类似物。

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