Carborane clusters increase the potency of bis-substituted cyclam derivatives against Mycobacterium tuberculosis .

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 MIC 50 values of <1 μM, making them the most active compounds in this unique class of antibacterial cyclams reported to date.