title: 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(37) Rv 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 μm while compounds 4, 6 and 8 displayed MIC activity at 1 < MIC<10 μM against H(37) Rv 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 μM against multi-drug resistant strain (R1097) and <1 μM 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 μM. This study demonstrates the first reported analysis of pentacyclo[5.3.0.0 ²,⁵.0³,⁹.0⁴,⁸]decane as a potential therapeutic agent.
authors.forename: Oluseye K
authors.initials: OK
authors.lastname: Onajole
authors.forename: Sphelele
authors.initials: S
authors.lastname: Sosibo
authors.forename: Patrick
authors.initials: P
authors.lastname: Govender
authors.forename: Thavendran
authors.initials: T
authors.lastname: Govender
authors.forename: Paul D
authors.initials: PD
authors.lastname: van Helden
authors.forename: Glenn E M
authors.initials: GE
authors.lastname: Maguire
authors.forename: Kata
authors.initials: K
authors.lastname: Mlinarić-Majerski
authors.forename: Ian
authors.initials: I
authors.lastname: Wiid
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Kruger
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology*; D003959:Diamines / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011083:Polycyclic Compounds / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D003959:Diamines; D011083:Polycyclic Compounds