New Promising Compounds with in Vitro Nanomolar Activity against Trypanosoma cruzi

Laura Friggeri; Luigi Scipione; Roberta Costi; Marcel Kaiser; Francesca Moraca; Claudio Zamperini; Bruno Botta; Roberto Di Santo; Daniela De Vita; Reto Brun; Silvano Tortorella

doi:10.1021/ml400039r

New Promising Compounds with in Vitro Nanomolar Activity against Trypanosoma cruzi

ACS Med Chem Lett. 2013 May 7;4(6):538-41. doi: 10.1021/ml400039r. eCollection 2013 Jun 13.

Authors

Affiliations

¹ Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma , P.le A. Moro 5, 00185 Rome, Italy.
² Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma , P.le A. Moro 5, 00185 Rome, Italy.
³ Department Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute , Socinstrasse 57, CH-4051 Basel, Switzerland.
⁴ Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena , Via A. Moro 2, 53100 Siena, Italy.
⁵ Department Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute , Socinstrasse 57, CH-4051 Basel, Switzerland ; University of Basel , Petersplatz 1, CH-4003 Basel, Switzerland.

Abstract

The antiparasitic activity of azole and new 4-aminopyridine derivatives has been investigated. The imidazoles 1 and 3-5 showed a potent in vitro antichagasic activity with IC50 values in the low nanomolar concentration range. The (S)-1, (S)-3, and (S)-5 enantiomers showed (up to) a thousand-fold higher activity than the reference drug benznidazole and furthermore low cytotoxicity on rat myogenic L6 cells.

Keywords: CYP51; Chagas disease; Trypanosoma cruzi; aminopyridine; antiparasitic activity; azole.