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

  • Bioorg Med Chem Lett. 2014 Mar 1;24(5):1358-61. doi: 10.1016/j.bmcl.2014.01.039.
Patrícia de Oliveira Figueiredo  1 ,  Renata Trentin Perdomo  2 ,  Fernanda Rodrigues Garcez  3 ,  Maria de Fatima Cepa Matos  4 ,  João Ernesto de Carvalho  5 ,  Walmir Silva Garcez  6
Affiliations
  • 1. Instituto de Química, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS 79074-460, Brazil. Electronic address: [email protected].
  • 2. Centro de Ciências Biológicas e da Saúde, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS 79070-900, Brazil. Electronic address: [email protected].
  • 3. Instituto de Química, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS 79074-460, Brazil. Electronic address: [email protected].
  • 4. Centro de Ciências Biológicas e da Saúde, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS 79070-900, Brazil. Electronic address: [email protected].
  • 5. Centro Pluridisciplinar de Pesquisas Químicas Biológicas e Agrícolas, Universidade Estadual de Campinas, Campinas, SP 13081-970, Brazil. Electronic address: [email protected].
  • 6. Instituto de Química, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS 79074-460, Brazil. Electronic address: [email protected].
PMID: 24507920 DOI: 10.1016/j.bmcl.2014.01.039
Abstract

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.

Keywords
Galianthe; Galianthe thalictroides; SRB assay; Topoisomerase; β-Carboline alkaloids.