Further constituents of Galianthe thalictroides (Rubiaceae) and inhibition of DNA topoisomerases I and II alpha by its cytotoxic beta-carboline alkaloids

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)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.24513581361Fundect-MSCPq-PROPP-UFMSCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq