Synthesis and biological evaluation of quinoxaline di-N-oxide derivatives with in vitro trypanocidal activity

Silvia Pérez-Silanes; Enrique Torres; Leire Arbillaga; Javier Varela; Hugo Cerecetto; Mercedes González; Amaya Azqueta; Elsa Moreno-Viguri

doi:10.1016/j.bmcl.2015.12.070

Synthesis and biological evaluation of quinoxaline di-N-oxide derivatives with in vitro trypanocidal activity

Bioorg Med Chem Lett. 2016 Feb 1;26(3):903-906. doi: 10.1016/j.bmcl.2015.12.070. Epub 2015 Dec 21.

Authors

Silvia Pérez-Silanes¹, Enrique Torres², Leire Arbillaga³, Javier Varela⁴, Hugo Cerecetto⁴, Mercedes González⁴, Amaya Azqueta⁵, Elsa Moreno-Viguri⁶

Affiliations

¹ Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain; Institute of Tropical Health, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain.
² Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain.
³ Department of Pharmacology and Toxicology, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain.
⁴ Grupo de Química Medicinal, Laboratorio de Química Orgánica, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay.
⁵ Department of Pharmacology and Toxicology, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Recinto de Complejo Hospitalario de Navarra c/Irunlarrea 3, Pamplona 31008, Spain.
⁶ Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain; Institute of Tropical Health, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain. Electronic address: emviguri@unav.es.

PMID: 26750255
DOI: 10.1016/j.bmcl.2015.12.070

Abstract

We report the synthesis and in vitro activity against Trypanosoma cruzi epimastigotes of 15 novel quinoxaline derivatives. Ten of the derivatives presented IC50 values lower than the reference drugs Nfx and Bzn; four of them standed out with IC50 values lower than 1.5 μM. Moreover, unspecific cytotoxicity and genotoxicity studies are also reported. Compound 14 showed a SI higher than 24, whereas compound 10 was the only one that was negative in the genotoxicity screening.

Keywords: Chagas disease; Cytotoxicity; Genotoxicity; Quinoxaline N-oxide; Trypanosoma cruzi.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Survival / drug effects
Chlorocebus aethiops
Nitrogen / chemistry
Oxides / chemistry
Quinoxalines / chemical synthesis
Quinoxalines / chemistry*
Quinoxalines / pharmacology
Structure-Activity Relationship
Trypanocidal Agents / chemical synthesis*
Trypanocidal Agents / chemistry
Trypanocidal Agents / pharmacology
Trypanosoma cruzi / drug effects
Vero Cells

Substances

Oxides
Quinoxalines
Trypanocidal Agents
quindoxin
Nitrogen