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.
Laura Friggeri  1 ,  Luigi Scipione  1 ,  Roberta Costi  2 ,  Marcel Kaiser  3 ,  Francesca Moraca  4 ,  Claudio Zamperini  4 ,  Bruno Botta  1 ,  Roberto Di Santo  2 ,  Daniela De Vita  1 ,  Reto Brun  5 ,  Silvano Tortorella  1
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.
PMID: 24900706 DOI: 10.1021/ml400039r
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.