In vitro activity of (-)-deoxypergularinine, on its own and in combination with anti-tubercular drugs, against resistant strains of Mycobacterium tuberculosis
- Authors
- Nam, Kung-Woo; Jang, Woong Sik; Jyoti, Md. Anirban; Kim, Sukyung; Lee, Byung-Eui; Song, Ho-Yeon
- Issue Date
- 15-May-2016
- Publisher
- Elsevier BV
- Keywords
- Antituberculosis drug; (-)-Deoxypergularinine; Synergy; Rifampicin; Isoniazid
- Citation
- Phytomedicine, v.23, no.5, pp 578 - 582
- Pages
- 5
- Journal Title
- Phytomedicine
- Volume
- 23
- Number
- 5
- Start Page
- 578
- End Page
- 582
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/9115
- DOI
- 10.1016/j.phymed.2016.02.017
- ISSN
- 0944-7113
- Abstract
- Background: The increasing incidence of multidrug-resistant tuberculosis (MDR-TB) infections has created a need for new effective drugs that also target extensively drug-resistant tuberculosis (XDR-TB) and/or augment the activities of existing drugs against tuberculosis. Aim: This study searched natural products for a new lead compound that targets MDR/XDR-TB. Methods: An active compound was purified from the roots of Cynanchum atratum Bunge (Asclepiadaceae) after screening 1640 plant extracts, and its inhibitory effects against MDR/XDR strains and synergistic effects with existing anti-TB drugs were assessed using the resazurin, MGIT, and checkboard assays. Results: (-)-Deoxypergularinine, purified from the roots of C. atratum, inhibited not only M. tuberculosis but also MDR/XDR strains. The minimum inhibitory concentrations (MICs) of (-)-deoxypergularinine for H37Ra, H37Rv, MDR, and XDR strains were all about 12.5 mu g/ml. Moreover, combinations of (-)-deoxypergularinine with the first-line standard drugs rifampicin or isoniazid afforded six-and eight-fold reductions in drug MIC values, respectively, against strain H37Ra. Conclusions: (-)-Deoxypergularinine exerts anti-tubercular activities not only against normal tuberculosis strains but also MDR/XDR strains, and synergic effects with rifampicin and isoniazid for the H37Ra strain. The alkaloid may be valuable for targeting M/XDR M. tuberculosis. (C) 2016 Elsevier GmbH. All rights reserved.
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