title: Identification of Bostrycin Derivatives as Potential Inhibitors of Mycobacterium tuberculosis Protein Tyrosine Phosphatase (MptpB).
abstract: BACKGROUND
  As a virulence factor secreted into host cells, the Mycobacterium tuberculosis protein tyrosine phosphatase (MptpB) mediates the intracellular survival of M. tuberculosis. MptpB has become an attractive target for the development of new anti-tuberculosis drugs.
  
  
  OBJECTIVE
  In the present study, we assessed the inhibitory activity of marine fungus-derived bostrycin and its derivatives against MptpB in vitro.
  
  
  METHODS
  The compounds were tested for their inhibitory effects on MptpB in vitro and the inhibition mode. The binding characteristics of inhibitors and MptpB were determined by microscale thermophoresis (MST).
  
  
  RESULTS
  Our data showed that one of the derivatives, compound 25 (IC50 = 64.6 ± 9.1 µM), possessed a greater inhibitory activity compared with bostrycin (IC50 = 327.6 ± 60.4 µM) and behaved as a non-competitive inhibitor. The binding characteristic of MptpB and compound 25 was determined by MST, exhibiting a moderate affinity with a KD constant of 5200 ± 1020 nM.
  
  
  CONCLUSIONS
  We, for the first time, reported that bostrycin and one of its analogues exhibited inhibitory activity against MptpB, which possessed potential as novel agents against tuberculosis.
authors.forename: Dong-ni
authors.initials: DN
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Zhi-gang
authors.initials: ZG
authors.lastname: She
authors.affiliation: School of Life Sciences, Sun Yat-sen university, 135 West Xingang Road, Guangzhou, Guangdong 510275, People's Republic of China. luyj@mail.sysu.edu.cn.
authors.forename: Yong-jun
authors.initials: YJ
authors.lastname: Lu
mesh_terms: D000880:Anthraquinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; C034287:bostrycin; D017027:Protein Tyrosine Phosphatases