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Antimicrobial Agents and Chemotherapy, September 2009, p. 3815-3821, Vol. 53, No. 9
0066-4804/09/$08.00+0     doi:10.1128/AAC.00124-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Antiprotozoal Activity of 1-Phenethyl-4-Aminopiperidine Derivatives {triangledown}

Christophe Dardonville,1* Cristina Fernández-Fernández,1 Sarah-Louise Gibbons,1 Nadine Jagerovic,1 Lidia Nieto,1 Gary Ryan,1 Marcel Kaiser,2 and Reto Brun1

Instituto de Química Médica, CSIC, Juan de la Cierva 3, E-28006 Madrid, Spain,1 Swiss Tropical Institute, Socinstrasse, 57, CH-4002 Basel, Switzerland2

Received 28 January 2009/ Returned for modification 12 April 2009/ Accepted 24 June 2009

A series of 44 4-aminopiperidine derivatives was screened in vitro against four protozoan parasites (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum). This screening identified 29 molecules selectively active against bloodstream-form T. b. rhodesiense trypomastigotes, with 50% inhibitory concentrations (IC50) ranging from 0.12 to 10 µM, and 33 compounds active against the chloroquine- and pyrimethamine-resistant K1 strain of P. falciparum (IC50 range, 0.17 to 5 µM). In addition, seven compounds displayed activity against intracellular T. cruzi amastigotes in the same range as the reference drug benznidazole (IC50, 1.97 µM) but were also cytotoxic to L-6 cells, showing little selectivity for T. cruzi. None of the molecules tested showed interesting antileishmanial activity against axenic amastigotes of L. donovani. To our knowledge, this is the first report of the antitrypanosomal activity of molecules bearing the 4-aminopiperidine skeleton.

* Corresponding author. Mailing address: Instituto de Química Médica, CSIC, Juan de la Cierva 3, E-28006 Madrid, Spain. Phone: 34 912587490. Fax: 34 915644853. E-mail: dardonville{at}iqm.csic.es

{triangledown} Published ahead of print on 29 June 2009.

Antimicrobial Agents and Chemotherapy, September 2009, p. 3815-3821, Vol. 53, No. 9
0066-4804/09/$08.00+0     doi:10.1128/AAC.00124-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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