Linked Life Data

21126020

Source:http://linkedlifedata.com/resource/pubmed/id/21126020

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pubmed-article:21126020pubmed:abstractTextLibraries of novel trisubstituted benzimidazoles were created through rational drug design. A good number of these benzimidazoles exhibited promising MIC values in the range of 0.5-6 ?g/mL (2-15 ?M) for their antibacterial activity against Mtb H37Rv strain. Moreover, five of the lead compounds also exhibited excellent activity against clinical Mtb strains with different drug-resistance profiles. All lead compounds did not show appreciable cytotoxicity (IC(50) > 200 ?M) against Vero cells, which inhibited Mtb FtsZ assembly in a dose dependent manner. The two lead compounds unexpectedly showed enhancement of the GTPase activity of Mtb FtsZ. The result strongly suggests that the increased GTPase activity destabilizes FtsZ assembly, leading to efficient inhibition of FtsZ polymerization and filament formation. The TEM and SEM analyses of Mtb FtsZ and Mtb cells, respectively, treated with a lead compound strongly suggest that lead benzimidazoles have a novel mechanism of action on the inhibition of Mtb FtsZ assembly and Z-ring formation.lld:pubmed
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pubmed-article:21126020pubmed:articleTitleNovel trisubstituted benzimidazoles, targeting Mtb FtsZ, as a new class of antitubercular agents.lld:pubmed
pubmed-article:21126020pubmed:affiliationDepartment of Chemistry, State University of New York at Stony Brook, Stony Brook, New York 11794-3400, United States.lld:pubmed
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