Abstract
A series of polycyclic ‘cage’ derivatives of N-geranyl-1,2 diamines were synthesized and screened for their anti-mycobacterial activity against H37Rv, 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.
Using the BACTEC MGIT 960 system, compound 9 (trishomocubanyl moiety) proved to be the most activity (MICs:0.5–2 μg/mL) while PCU hydroxyl derivative(15 and 23), oxa-pentacycloundecyl and azapentacycloundecyl derivative displayed similar activity as SQ109(MIC: 0.5–4 μg/mL) against all three strains of TB used in this study. [Display omitted]
► Synthesis of novel polycyclic ‘cage’-1,2-diamines derivatives were reported. ► Four novel compounds showed potent anti-tuberculosis activities in vitro. ► Compound 9 displayed potent activity in vitro against MDR and XDR strains of TB.