Further constituents of Galianthe thalictroides (Rubiaceae) and inhibition of DNA topoisomerases I and IIα by its cytotoxic β-carboline alkaloids

被引:34
作者
Figueiredo, Patricia de Oliveira [1 ]
Perdomo, Renata Trentin [2 ]
Garcez, Fernanda Rodrigues [1 ]
Cepa Matos, Maria de Fatima [2 ]
de Carvalho, Joao Ernesto [3 ]
Garcez, Walmir Silva [1 ]
机构
[1] Univ Fed Mato Grosso do Sul, Inst Quim, BR-79074460 Campo Grande, MS, Brazil
[2] Univ Fed Mato Grosso do Sul, Ctr Ciencias Biol & Saude, BR-79070900 Campo Grande, MS, Brazil
[3] Univ Estadual Campinas, Ctr Pluridisciplinar Pesquisas Quim Biol & Agr, BR-13081970 Campinas, SP, Brazil
关键词
Galianthe; Galianthe thalictroides; beta-Carboline alkaloids; Topoisomerase; SRB assay; ANTITUMOR AGENTS; CHEMICAL-CONSTITUENTS; ANTICANCER; DERIVATIVES; EXTRACT; HARMINE; ETHER;
D O I
10.1016/j.bmcl.2014.01.039
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A new cytotoxic beta-carboline alkaloid, 1-methyl-3-(2-hydroxypropan-2-yl)-2-(5-methoxy-9H-beta-carbolin-1-yl)-cyclopentanol (1), was isolated from roots of Galianthe thalictroides, together with the alkaloid 1-(hydroxymethyl)-3-(2-hydroxypropan-2-yl)-2-(5-methoxy-9H-beta-carbolin-1-yl)-cyclopentanol (2), the anthraquinones 1-methyl-alizarin and morindaparvin-A, the coumarin scopoletin, homovanillic alcohol, (-)-epicatechin, and the steroids stigmast-4-en-3-one, 4,22-stigmastadien-3-one, campest-4-en-3-one, stigmast-4-en-3,6-dione, 6-beta-hydroxy-stigmast-4-en-3-one, stigmasterol, campesterol, beta-sitosterol, and beta-sitosterol-3-O-beta-D-glucopyranoside. Among the previously known compounds, homovanillic alcohol is a novel finding in Rubiaceae, while 1-methyl-alizarin, morindaparvin-A, scopoletin, stigmast-4-en-3-one, 4,22-stigmastadien-3-one, campest-4-en-3-one, stigmast-4-en-3,6-dione, and 6-beta-hydroxy-stigmast-4-en-3-one is reported for the first time in the genus Galianthe. The cytotoxic beta-carboline alkaloids 1 and 2 exhibited potent antitopoisomerase I and IIa activities and strong evidence is provided for their action as topoisomerase IIa poisons and redox-independent inhibitors. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1358 / 1361
页数:4
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