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

• Published in: Bioorganic & medicinal chemistry letters 2014-03, Vol.24 (5), p.1358-1361
• Main Authors: de Oliveira Figueiredo, Patrícia, Perdomo, Renata Trentin, Garcez, Fernanda Rodrigues, de Fatima Cepa Matos, Maria, de Carvalho, João Ernesto, Garcez, Walmir Silva
• Format: Article
• Language: English
• Subjects: Alkaloids - chemistry; Alkaloids - isolation & purification; Alkaloids - toxicity; Animals; Antigens, Neoplasm - metabolism; Cell Line, Tumor; Cell Survival - drug effects; DNA Topoisomerases, Type I - chemistry; DNA Topoisomerases, Type I - metabolism; DNA Topoisomerases, Type II - metabolism; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - metabolism; Humans; Lactose - analogs & derivatives; Lactose - chemical synthesis; Lactose - chemistry; Lactose - pharmacokinetics; MCF-7 Cells; Mice; Oligopeptides - chemical synthesis; Oligopeptides - chemistry; Oligopeptides - pharmacokinetics; Plant Roots - chemistry; Plant Roots - metabolism; Rubiaceae; Rubiaceae - chemistry; Rubiaceae - metabolism; Topoisomerase Inhibitors - chemistry; Topoisomerase Inhibitors - isolation & purification; Topoisomerase Inhibitors - toxicity
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2014.01.039

A new cytotoxic β-carboline alkaloid, 1-methyl-3-(2-hydroxypropan-2-yl)-2-(5-methoxy-9H-β-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-β-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-β-hydroxy-stigmast-4-en-3-one, stigmasterol, campesterol, β-sitosterol, and β-sitosterol-3-O-β-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-β-hydroxy-stigmast-4-en-3-one is reported for the first time in the genus Galianthe. The cytotoxic β-carboline alkaloids 1 and 2 exhibited potent antitopoisomerase I and IIα activities and strong evidence is provided for their action as topoisomerase IIα poisons and redox-independent inhibitors.