Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Med Chem. 2011 Jan 13;54(1):374-81. doi: 10.1021/jm1012006. Epub 2010 Dec 2.

Novel trisubstituted benzimidazoles, targeting Mtb FtsZ, as a new class of antitubercular agents.

Author information

  • 1Department of Chemistry, State University of New York at Stony Brook, Stony Brook, New York 11794-3400, United States.

Abstract

Libraries 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 μg/mL (2-15 μM) 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 μM) 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.

PMID:
21126020
[PubMed - indexed for MEDLINE]
PMCID:
PMC3071426
Free PMC Article

Images from this publication.See all images (8)Free text

Figure 1
Scheme 1
Scheme 2
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for American Chemical Society Icon for PubMed Central
    Loading ...
    Write to the Help Desk