Nontoxic Metal-Cyclam Complexes, a New Class of Compounds with Potency against Drug-Resistant Mycobacterium tuberculosis

J Med Chem. 2016 Jun 23;59(12):5917-21. doi: 10.1021/acs.jmedchem.6b00432. Epub 2016 Jun 7.

Abstract

Tuberculosis (TB) accounted for 1.5 million deaths in 2014, and new classes of anti-TB drugs are required. We report a class of functionalized 1,8-disubstituted cyclam derivatives that display low micromolar activity against pathogenic mycobacteria. These compounds inhibit intracellular growth of Mycobacterium tuberculosis, are nontoxic to human cell lines, and are active against multidrug-resistant M. tuberculosis strains, indicating a distinct mode of action. These compounds warrant further appraisal as novel agents to control TB in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Conformation
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / growth & development
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Structure-Activity Relationship
  • Tuberculosis, Multidrug-Resistant / drug therapy*

Substances

  • Antitubercular Agents
  • Organometallic Compounds