title: In vitro activity of (-)-deoxypergularinine, on its own and in combination with anti-tubercular drugs, against resistant strains of Mycobacterium tuberculosis.
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.
  
  
  OBJECTIVE
  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 µg/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.
authors.affiliation: Department of Life Science and Biotechnology, School of Life Sciences, Soonchunhyang University, Asan, Chungnam 31538, Republic of Korea. Electronic address: kwnam1@sch.ac.kr.
authors.forename: Kung-Woo
authors.initials: KW
authors.lastname: Nam
authors.affiliation: Regional Innovation Center, Soonchunhyang University, Asan, Chungnam 31538, Republic of Korea.
authors.forename: Woong Sik
authors.initials: WS
authors.lastname: Jang
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, Cheonan, Chungnam 31538, Republic of Korea.
authors.forename: Md Anirban
authors.initials: MA
authors.lastname: Jyoti
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, Cheonan, Chungnam 31538, Republic of Korea.
authors.forename: Sukyung
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Chemistry, School of Life Sciences, Soonchunhyang University, Asan, Chungnam 31538, Republic of Korea.
authors.forename: Byung-Eui
authors.initials: BE
authors.lastname: Lee
authors.affiliation: Regional Innovation Center, Soonchunhyang University, Asan, Chungnam 31538, Republic of Korea; Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, Cheonan, Chungnam 31538, Republic of Korea. Electronic address: songmic@sch.ac.kr.
authors.forename: Ho-Yeon
authors.initials: HY
authors.lastname: Song
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D031105:Cynanchum / Q000737:chemistry; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D054908:Extensively Drug-Resistant Tuberculosis; D007538:Isoniazid / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D012293:Rifampin / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D007546:Isoquinolines; D010936:Plant Extracts; C000611652:deoxypergularinine; D007538:Isoniazid; D012293:Rifampin
keywords: (-)-Deoxypergularinine; Antituberculosis drug; Isoniazid; Rifampicin; Synergy