Novel polycyclic 'cage'-1,2-diamines as potential anti-tuberculosis agents.
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.
School of Chemistry, University of KwaZulu-Natal, Durban, South Africa.
Oluseye K
OK
Onajole
Yacoob
Y
Coovadia
Hendrik G
HG
Kruger
Glenn E M
GE
Maguire
Melendhran
M
Pillay
Thavendran
T
Govender
D000473:Alkanes / Q000737:chemistry; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011083:Polycyclic Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000473:Alkanes; D000995:Antitubercular Agents; D003959:Diamines; D011083:Polycyclic Compounds; C022884:undecane