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一种双苯并吡咯异喹啉生物碱,具有中环丁烷核和来源于榕属天仙果变种的细胞毒性的氯菲并吲嗪生物碱。

A Bis-benzopyrroloisoquinoline Alkaloid Incorporating a Cyclobutane Core and a Chlorophenanthroindolizidine Alkaloid with Cytotoxic Activity from Ficus fistulosa var. tengerensis.

机构信息

School of Pharmacy, University of Nottingham Malaysia Campus , Jalan Broga, 43500 Semenyih, Selangor, Malaysia.

School of Pharmacy, International Medical University , Bukit Jalil, 57000 Kuala Lumpur, Malaysia.

出版信息

J Nat Prod. 2017 Oct 27;80(10):2734-2740. doi: 10.1021/acs.jnatprod.7b00500. Epub 2017 Sep 19.

Abstract

Tengerensine (1), isolated as a racemate and constituted from a pair of bis-benzopyrroloisoquinoline enantiomers, and tengechlorenine (2), purified as a scalemic mixture and constituted from a pair of chlorinated phenanthroindolizidine enantiomers, were isolated from the leaves of Ficus fistulosa var. tengerensis, along with three other known alkaloids. The structures of 1 and 2 were determined by spectroscopic data interpretation and X-ray diffraction analysis. The enantiomers of 1 were separated by chiral-phase HPLC, and the absolute configurations of (+)-1 and (-)-1 were established via experimental and calculated ECD data. Compound 1 is notable in being a rare unsymmetrical cyclobutane adduct and is the first example of a dimeric benzopyrroloisoquinoline alkaloid, while compound 2 represents the first naturally occurring halogenated phenanthroindolizidine alkaloid. Compound (+)-1 displayed a selective in vitro cytotoxic effect against MDA-MB-468 cells (IC 7.4 μM), while compound 2 showed pronounced in vitro cytotoxic activity against all three breast cancer cell lines tested (MDA-MB-468, MDA-MB-231, and MCF7; IC values of 0.038-0.91 μM).

摘要

从中国南方的天仙果叶(Ficus fistulosa var. tengerensis)中分离得到了天名精素(1)和天名精氯灵(2),它们分别是一对对映体的双苯并吡咯异喹啉生物碱和一对对映体的氯化菲并吲哚里西啶生物碱。1 和 2 的结构通过光谱数据分析和 X 射线衍射分析确定。通过手性相高效液相色谱法分离出 1 的对映异构体,并通过实验和计算的 ECD 数据确定了 (+)-1 和 (-)-1 的绝对构型。1 是一种罕见的非对称环丁烷加合物,是首例二聚苯并吡咯异喹啉生物碱,而 2 则是首例天然存在的卤化菲并吲哚里西啶生物碱。化合物 (+)-1 对 MDA-MB-468 细胞具有选择性的体外细胞毒性作用(IC 7.4 μM),而化合物 2 对三种测试的乳腺癌细胞系(MDA-MB-468、MDA-MB-231 和 MCF7)均具有显著的体外细胞毒性作用(IC 值为 0.038-0.91 μM)。

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