title: A protein kinase inhibitor as an antimycobacterial agent.
abstract: The protein kinase inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) was found to inhibit the growth of two different mycobacterial strains, the slow-growing Mycobacterium bovis Bacille Calmette Guerin (BCG) and the fast-growing saprophyte Mycobacterium smegmatis mc2 155, in a dose-dependent manner. While screening for the effect of kinase inhibitors on mycobacterial growth, millimolar concentrations of H7 induced a 40% decrease in the growth of M. bovis BCG when measured as a function of oxidative phosphorylation. This H7-induced decrease in growth was shown to involve a 2-log fold decrease in the viable counts of M. smegmatis within a 48-h period and a 50% reduction in the number of BCG viable counts within a 10-day period. Micromolar concentrations of H7 compound induced a significant decrease in the activity of the Mycobacterium tuberculosis protein serine/threonine kinase (PSTK) PknB. The inhibition of mycobacterial growth as well as the inhibition of a representative M. tuberculosis protein serine/threonine kinase PknB suggests that conventional PSTK inhibitors can be used to study the role that the mycobacterial PSTK family plays in controlling bacterial growth.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of British Columbia, V5Z 3J5, Vancouver, BC, Canada.
authors.forename: S J
authors.initials: SJ
authors.lastname: Drews
authors.forename: F
authors.initials: F
authors.lastname: Hung
authors.forename: Y
authors.initials: Y
authors.lastname: Av-Gay
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D047908:Intracellular Signaling Peptides and Proteins; D009163:Mycobacterium bovis / Q000187:drug effects* / Q000201:enzymology; D020102:Mycobacterium smegmatis / Q000187:drug effects* / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C015482:protein kinase modulator; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases