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从多叶唐松草中分离出的一种新的双苄基异喹啉生物碱,作为杜氏利什曼原虫DNA拓扑异构酶IB的有效抑制剂。

A new bisbenzylisoquinoline alkaloid isolated from Thalictrum foliolosum, as a potent inhibitor of DNA topoisomerase IB of Leishmania donovani.

作者信息

Kumar Ashish, Chowdhury Somenath Roy, Sarkar Tapas, Chakrabarti Tulika, Majumder Hemanta K, Jha Tarun, Mukhopadhyay Sibabrata

机构信息

Chemistry Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata - 700032, India.

Molecular Parasitology Laboratory, Infectious Diseases & Immunology Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata - 700032, India.

出版信息

Fitoterapia. 2016 Mar;109:25-30. doi: 10.1016/j.fitote.2015.11.021. Epub 2015 Nov 26.

Abstract

Chemical investigation of the stem of Thalictrum foliolosum resulted in the isolation of two new bisbenzylisoquinoline alkaloids (1 and 2) along with known protoberberine group of isoquinoline alkaloids thalifendine (3) and berberine (4). The structures of the new compounds were established by detailed 2D NMR spectral analysis with their configurations determined from their optical rotation values and confirmed using circular dichroism. Inhibitory activities of these four compounds against DNA topoisomerase IB of Leishmania donovani were evaluated. Compound 2 exhibited almost complete inhibition of the enzyme activity at 50 μM concentration and it was found to be effective in killing both wild type as well as SAG resistant promastigotes of the parasite.

摘要

对唐松草的茎进行化学研究,结果分离出两种新的双苄基异喹啉生物碱(1和2),以及已知的原小檗碱类异喹啉生物碱唐松芬定(3)和小檗碱(4)。通过详细的二维核磁共振光谱分析确定了新化合物的结构,其构型由旋光值确定,并通过圆二色性进行了确认。评估了这四种化合物对杜氏利什曼原虫DNA拓扑异构酶IB的抑制活性。化合物2在50μM浓度下几乎完全抑制了酶活性,并且发现它对该寄生虫的野生型以及SAG抗性前鞭毛体均有杀伤作用。

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