Structure-activity relationship studies on 2,5,6-trisubstituted benzimidazoles targeting -FtsZ as antitubercular agents.

Journal: RSC medicinal chemistry
Published Date:

Abstract

Filamenting temperature sensitive protein Z (FtsZ) is an essential bacterial cell division protein and a promising target for the development of new antibacterial therapeutics. As a part of our ongoing SAR studies on 2,5,6-trisubstituted benzimidazoles as antitubercular agents targeting -FtsZ, a new library of compounds with modifications at the 2 position was designed, synthesized and evaluated for their activity against -H37Rv. This new library of trisubstituted benzimidazoles exhibited MIC values in the range of 0.004-50 μg mL. Compounds , , and showed excellent growth inhibitory activities ranging from 0.004-0.08 μg mL. This SAR study has led to the discovery of a remarkably potent compound (MIC 0.0039 μg mL; normalized MIC 0.015 μg mL). Our 3DQSAR model predicted as the most potent compound in the library.

Authors

  • Krupanandan Haranahalli
    Institute of Chemical Biology and Drug Discovery, Stony Brook University Stony Brook NY USA iwao.ojima@stonybrook.edu.
  • Simon Tong
    Department of Chemistry, Stony Brook University Stony Brook NY USA.
  • Saerom Kim
    Department of Chemistry, Stony Brook University Stony Brook NY USA.
  • Monaf Awwa
    Department of Chemistry, Stony Brook University Stony Brook NY USA.
  • Lei Chen
    Department of Chemistry, Stony Brook University Stony Brook NY USA.
  • Susan E Knudson
    Department of Microbiology, Immunology and Pathology, Colorado State University Fort Collins Colorado 80523-1682 USA.
  • Richard A Slayden
    Department of Microbiology, Immunology and Pathology, Colorado State University Fort Collins Colorado 80523-1682 USA.
  • Eric Singleton
    Department of Medicine, Center for Emerging and Re-emerging Pathogens, Rutgers University Newark New Jersey 07103 USA.
  • Riccardo Russo
    Department of Medicine, Center for Emerging and Re-emerging Pathogens, Rutgers University Newark New Jersey 07103 USA.
  • Nancy Connell
    Department of Medicine, Center for Emerging and Re-emerging Pathogens, Rutgers University Newark New Jersey 07103 USA.
  • Iwao Ojima
    Institute of Chemical Biology and Drug Discovery, Stony Brook University Stony Brook NY USA iwao.ojima@stonybrook.edu.

Keywords

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