Antitubercular Bis-Substituted Cyclam Derivatives: Structure–Activity Relationships and in Vivo Studies

We recently reported the discovery of nontoxic cyclam-derived compounds that are active against drug-resistant Mycobacterium tuberculosis. In this paper we report exploration of the structure–activity relationship for this class of compounds, identifying several simpler compounds with comparable activity. The most promising compound identified, possessing significantly improved water solubility, displayed high levels of bacterial clearance in an in vivo zebrafish embryo model, suggesting this compound series has promise for in vivo treatment of tuberculosis.