Dong-ni Chen, Hong Chen, Zhi-gang She and Yong-jun Lu Pages 296 - 302 ( 7 )
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.
Method: 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.
Conclusion: 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.
Bostrycin, inhibitors, tyrosine phosphatase, anti-tuberculosis, microscale thermophoresis.
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