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DOI: 10.1055/s-0031-1300412
In vitro and in vivo Activity of K-130, a Dihydrofolate Reductase inhibitor, against Mycobacterium leprae
Publication History
Publication Date:
28 December 2011 (online)
Summary
The antimicrobial effects of a new dihydrofolate reductase inhibitor, K-130 (2,4-diaminodiphenyl sulfone substituted 2,4-diamino-5-benzylpyrimidine), alone and in combination with dapsone (CAS 80-08-0) against both dapsone-sensitive and dapsone-resistant strains of Mycobacterium leprae were evaluated in vitro, in cell-free culture system, and in vivo, in mouse foot pads. The minimal inhibitory concentration of K-130 against dapsone-sensitive as well as dapsone resistant strains of M. leprae was 0.03 μg/ml, and the activity was bactericidal in both cases. However, when combined with dapsone, K-130 exhibited synergism in case of dapsone-sensitive M. leprae, while in case of dapsone-resistant M. leprae, the effect was merely additive. Similar synergistic effects were also observed in the mouse foot pad system for both types of M. leprae strains.
Zusammenfassung
In-vitro- und In-vivo-Aktivität von K-130, einem Dihydrofolatreduktase-Inhibitor, gegen Mycobacterium leprae
Die antimikrobielle Wirkung des neuen Dihydrofolatreduktase-Inhibitors K-130 (2,4-Diaminodiphenylsulfon subst. 2,4-Diamino-5-benzylpyrimidin) allein und in Kombination mit Dapson (CAS 80-08-0) gegen Dapson-empfindliche sowie Dapson-resistente Mycobacterium leprae-Stämme wurde in vitro in einem zellfreien Kultursystem und in vivo am Mäusefuß Model1 untersucht. Die minimale Hemmkonzentration von K- 130 gegen Dapson-empfindliche und Dapson-resistente M. leprae-Stämme betrug 0,03 die Wirkung war in beiden Fällen bakterizid. Bei Kombination mit Dapson zeigte K-130 synergistische Wirkung gegen Dapsonempfindliche M. leprae-Stämme, gegen Dapson-resistente Stämme jedoch lediglich additive Wirkung. Vergleichbare additive Wirkung gegen beide M. leprae-Stämme war im Mäusefuß Modell zu beobachten.