<i>Mycobacterium </i>membrane protease as a target for inhibitors of intrabacterial pH homeostasis

摘要

The present invention is directed to methods and compounds for inhibiting bacterial growth and treating a bacterial infection in a subject. These methods involve providing an inhibitor of intrabacterial pH homeostasis, including inhibitors of the Mycobacterium tuberculosis Rv3671c gene encoded membrane protease. Methods for identifying novel compounds that disrupt intrabacterial pH homeostasis and their use for inhibiting bacterial growth and treating a bacterial infection in a subject are also disclosed.

主权项

1. A method of inhibiting growth of Mycobacterium comprising:
exposing Mycobacterium to an agent selected from the group consisting of 6-(3-butyryl-2,6-dihydroxy-4-methoxy-5-methylbenzyl)-3,5-dihydroxy-4,6-dimethyl-2-(2-methylbutanoyl)cyclohexa-2,4-dienone; (Z)-2-(3-hydroxy-5-oxo-4-pentylfuran-2(5H)-ylidene) acetic acid; 4-(2-methylbutanoyloxy)-5-(octanoyloxy)-2-((3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)methyl)-6-(2,3,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yloxy)tetrahydro2H-pyran-3-yl decanoate; 2-hydroxy-4-methoxy-3-(3-methylbut-2-enyl)-6-pentylbenzoic acid; and 2-hydroxy-3-(2-hydroxy-3-methylbut-3-enyl)-4-methoxy-6-phenethylbenzoic acid under conditions effective to disrupt intrabacterial pH homeostasis and inhibit growth of the Mycobacterium.