Novel Linear Diamine Disubstituted Polycyclic 'Cage' Derivatives as Potential Antimycobacterial Candidates

作者：Onajole Oluseye K; Sosibo Sphelele; Govender Patrick; Govender Thavendran; van Helden Paul D; Maguire Glenn E M; Mlinaric Majerski Kata; Wiid Ian; Kruger Hendrik G^*

来源：Chemical Biology & Drug Design, 2011, 78(6): 1022-1030.

DOI：10.1111/j.1747-0285.2011.01242.x

• antituberculosis activity
• isoprenyl diamine
• pentacyclodecane
• pentacycloundecane and tricyclodecane
• SQ109

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 H37Rv 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 1 mu m while compounds 4, 6 and 8 displayed MIC activity at 1 < MIC<10 mu m against H37Rv strain of tuberculosis. Compounds 5, 7 and SQ109 were selected for further screening against, multi-drug resistant, (R1097) and extensively drug resistant, (X149) strains of tuberculosis. Compound 5 showed anti-TB activity of a MIC = 1 mu m against multi-drug resistant strain (R1097) and <1 mu M against extensively drug resistant strain (X149) while compound 7 and SQ109 showed excellent anti-TB activity against both drug-resistant strains at a MIC <1 mu m. This study demonstrates the first reported analysis of pentacyclo[5.3.0.02,5.03,9.04,8]decane as a potential therapeutic agent.

• 出版日期2011-12