Synthesis of marine-derived 3-alkylpyridinium alkaloids with potent antiprotozoal activity

Rodenko, B., Al-Salabi, M.I., Teka, I.A., Ho, W., El-Sabbagh, N., Ali, J.A.M., Ibrahim, H.M.S., Wanner, M.J., Koomen, G.-J. and De Koning, H.P. (2011) Synthesis of marine-derived 3-alkylpyridinium alkaloids with potent antiprotozoal activity. ACS Medicinal Chemistry Letters, 2(12), pp. 901-906. (doi:10.1021/ml200160k)

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Publisher's URL: http://dx.doi.org/10.1021/ml200160k

Abstract

Given the pressing need for new antiprotozoal drugs without cross-resistance with current (failing) chemotherapy, we have explored 3-tridecylpyridinium alkaloids (3TPAs), derivatives of viscosamine, as antiparasitic agents. We have developed a simple synthetic route toward viscosamine and related cyclic and linear monomers and oligomers. Evaluation for cytotoxicity on the protozoan parasites Trypanosoma brucei, Leishmania spp., and Plasmodium falciparum revealed several 3TPAs with antiprotozoal activity in the nanomolar range. Their promising selectivity index in vitro prompted us to study the dynamics of cytotoxicity on trypanosomes in more detail. Parasites were killed relatively slowly at therapeutically safe concentrations, in a process that did not target the cell cycle. Clearance of T. brucei cultures was observed at drug concentrations of 1-10 mµ M

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rodenko, Dr Boris and De Koning, Professor Harry
Authors: Rodenko, B., Al-Salabi, M.I., Teka, I.A., Ho, W., El-Sabbagh, N., Ali, J.A.M., Ibrahim, H.M.S., Wanner, M.J., Koomen, G.-J., and De Koning, H.P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:ACS Medicinal Chemistry Letters
ISSN:1948-5875
Published Online:11 October 2011

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