Novel linear diamine disubstituted polycyclic 'cage' derivatives as potential antimycobacterial candidates

Abstract

As a part of an ongoing project to develop highly potent antituberculosis therapeutics, a series novel polycyclic 'cage' tetra-amines were synthesized and screened for in-vitro antituberculosis activities against the H 37Rv strain of tuberculosis. Three disubstituted polycyclic moieties, namely pentacyclodecane, pentacycloundecane, and tricyclodecane, were used in this study. Compounds 5 and 7 showed similar activity to SQ109 at a MIC of 1μm while compounds 4, 6 and 8 displayed MIC activity at 1 <1μM against extensively drug resistant strain (X149) while compound 7 and SQ109 showed excellent anti-TB activity against both drug-resistant strains at a MIC <1μm. This study demonstrates the first reported analysis of pentacyclo[5.3.0.0 2,5.0 3,9.0 4,8]decane as a potential therapeutic agent. © 2011 John Wiley & Sons A/S.