Carborane clusters increase the potency of bis-substituted cyclam derivatives against Mycobacterium tuberculosis
Nicholas Smith1, Diana Quan2,3, Gayathri Nagalingam2,3
1School of Chemistry, The University of Sydney Sydney NSW 2006 Australia peter.rutledge@sydney.edu.au louis.rendina@sydney.edu.au +61 2 9351 5020 +61 2 9351 4781.
Abstract:
Bis-substituted cyclam derivatives have recently emerged as a promising new class of antibacterial agents, displaying excellent activity against drug-resistant Mycobacterium tuberculosis (Mtb) and in vivo efficacy in a zebrafish assay. Herein we report the synthesis and biological activity of new carborane derivatives within this class of antitubercular compounds. The resulting carborane-cyclam conjugates incorporating either hydrophobic closo-1,2-carborane or anionic, hydrophilic nido-7,8-carborane clusters display promising activity in an antibacterial assay employing the virulent Mtb strain H37Rv. The most active of these carborane derivatives exhibit MIC50 values of <1 μM, making them the most active compounds in this unique class of antibacterial cyclams reported to date.
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