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ID: ALA2086347

Journal: Bioorg Med Chem Lett

Title: Antitrypanosomal and cysteine protease inhibitory activities of alkyldiamine cryptolepine derivatives.

Authors: Lavrado J, Mackey Z, Hansell E, McKerrow JH, Paulo A, Moreira R.

Abstract: Cryptolepine derivatives containing alkyldiamine side-chains, 2, with potent inhibitory activity against Trypanosoma brucei brucei are reported. Compounds 2 showed improved activity and selectivity to T. b. brucei when compared to the lead compound. The most selective compound, 2k, presents a selectivity index value of 6200 and an IC(50) of 10nM against the parasite. These derivatives are also potent inhibitors of the trypanosome papain-like cysteine proteases cruzain, which could, at least in part, explain their antitrypanosomal activity. Overall, these compounds with good antitrypanosomal activity and selectivity provide an encouraging starting point for the rational design of new and effective antitrypanosomal agents.

CiteXplore: 22926067

DOI: 10.1016/j.bmcl.2012.07.104