Anti-Tubercular bis-Substituted Cyclam Derivatives: Structure-Activity Relationships and In Vivo Studies
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Open Access
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ArticleAuthor/s
Spain, MalcolmWong, Joseph K.-H.
Nagalingam, Gayathri
Batten, James M.
Hortle, Elinor
Oehlers, Stefan
Jiang, Xiao Fan
Murage, Hasini E.
Orford, Jack T.
Crisologo, Patrick
Triccas, James A.
Rutledge, Peter J.
Todd, Matthew H.
Abstract
We recently reported the discovery of non-toxic 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.We recently reported the discovery of non-toxic 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.
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Date
2018-03-20Publisher
American Chemical SocietyCitation
Spain, M., Wong, J., Nagalingam, G., Batten, J., Hortle, E., Oehlers, S., Jiang, X., Murage, H., Orford, J., Crisologo, P., Triccas, J., Rutledge, P., Todd, M. (2018). Antitubercular bis-substituted cyclam derivatives: Structure-activity relationships and in vivo studies. Journal of Medicinal Chemistry, 61(8), 3595-3608.Share