Bioorganic & Medicinal Chemistry 2011-03-01

Huprines as a new family of dual acting trypanocidal-antiplasmodial agents.

Julien Defaux, Marta Sala, Xavier Formosa, Carles Galdeano, Martin C Taylor, Waleed A A Alobaid, John M Kelly, Colin W Wright, Pelayo Camps, Diego Muñoz-Torrero

Index: Bioorg. Med. Chem. 19(5) , 1702-7, (2011)

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Abstract

A series of 19 huprines has been evaluated for their activity against cultured bloodstream forms of Trypanosoma brucei and Plasmodium falciparum. Moreover, cytotoxicity against rat myoblast L6 cells was assessed for selected huprines. All the tested huprines are moderately potent and selective trypanocidal agents, exhibiting IC(50) values against T. brucei in the submicromolar to low micromolar range and selectivity indices for T. brucei over L6 cells of approximately 15, thus constituting interesting trypanocidal lead compounds. Two of these huprines were also found to be active against a chloroquine-resistant strain of P. falciparum, thus emerging as interesting trypanocidal-antiplasmodial dual acting compounds, but they exhibited little selectivity for P. falciparum over L6 cells.Copyright © 2011 Elsevier Ltd. All rights reserved.