Synthesis and evaluation of SQ109 analogues as potential anti-tuberculosis candidates

Eur J Med Chem. 2010 May;45(5):2075-9. doi: 10.1016/j.ejmech.2010.01.046. Epub 2010 Jan 28.

Abstract

As part of an ongoing project to develop highly potent anti-tuberculosis therapeutics, six SQ109 derivatives were synthesized and screened in vitro for their anti-tuberculosis activity against the ATCC strain H37Rv and the extensively drug-resistant clinical strain XDR 173. Compound 16 with an extended alkene chain was the most active against both strains of Mycobacterium tuberculosis within a MIC range of 0.5-0.25 microM. Compound 12 and SQ109 were potent within a MIC range of 1-0.5 microM, whilst compound 18 displayed an activity within the MIC range of 0.5-2 microM against both Mycobacterium tuberculosis strains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / chemical synthesis
  • Adamantane / chemistry
  • Adamantane / pharmacology
  • Antitubercular Agents / chemical synthesis*
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Ethylenediamines / chemical synthesis
  • Ethylenediamines / chemistry*
  • Ethylenediamines / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects*
  • Stereoisomerism

Substances

  • Antitubercular Agents
  • Ethylenediamines
  • N-geranyl-N'-(2-adamantyl)ethane-1,2-diamine
  • Adamantane