Novel polycyclic 'cage'-1,2-diamines as potential anti-tuberculosis agents

Eur J Med Chem. 2012 Aug:54:1-9. doi: 10.1016/j.ejmech.2012.03.041. Epub 2012 Apr 4.

Abstract

A series of polycyclic 'cage' derivatives of N-geranyl-1,2 diamines were synthesized and screened for their anti-mycobacterial activity against H(37)Rv, multidrug resistant (MDR) and extensively drug-resistant (XDR) strains of tuberculosis. By substituting the adamantyl skeleton of SQ109 with trishomocubanyl (9), oxa-pentacycloundecyl (14, 16), pentacycloundecyl, PCU, (10, 15) and azapentacycloundecyl (22, 23), the effect of other polycyclic "cage" skeletons could be investigated. Compound 9 (trishomocubanyl moiety) proved to be the most active (MICs: 0.5-2 μg/mL) while PCU hydroxyl derivatives (15 and 23), oxa-pentacycloundecyl and azapentacycloundecyl derivatives displayed similar activity to SQ109 (MICs: 0.5-4 μg/mL) against all three strains of TB used in this study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkanes / chemistry
  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry*
  • Antitubercular Agents / pharmacology*
  • Diamines / chemical synthesis
  • Diamines / chemistry*
  • Diamines / pharmacology*
  • Drug Resistance, Bacterial / drug effects
  • Drug Resistance, Multiple / drug effects
  • Hydrophobic and Hydrophilic Interactions
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects
  • Polycyclic Compounds / chemistry*
  • Structure-Activity Relationship

Substances

  • Alkanes
  • Antitubercular Agents
  • Diamines
  • Polycyclic Compounds
  • undecane