New aryloxy-quinone derivatives with promising activity on Trypanosoma cruzi

Espinosa-Bustos C.; Vázquez K.; Varela J.; Cerecetto, H.; Paulino M.; Segura R.; Pizarro J.; Vera B.; González M.; Zarate A.M.; Salas, C. O.

Abstract

Continuing with a program to develop new quinone derivatives as biologically active compounds, we designed and synthesized a new series of aryloxy-quinones, which were evaluated in vitro against Trypanosoma cruzi in epimastigote form. Chemical modifications in three specific moieties on the aryloxy-quinone core were considered for developing new anti-T. cruzi agents. The majority of our new quinones showed higher potency (IC50 values of <0.70 mu M) than nifurtimox, a known pharmaceutical used as a baseline drug (IC50 values of 7.00 mu M); however, only two of them elicited higher selectivity than nifurtimox against Vero cells. A structure-activity relationship analysis provided information about the stereoelectronic features of these compounds, which are responsible for an increase in trypanosomicidal activity. Using a pharmacophore model, we mapped the substitution patterns of the five pharmacophoric features of trypanosomicidal activity. We chose the E-pc1 compounds and found no relationship with the trypanosomicidal effects. These results provided useful information about the structural characteristics for developing new aryloxy-quinones with higher potency against the protozoan parasite T. cruzi.

Más información

Título según WOS: New aryloxy-quinone derivatives with promising activity on Trypanosoma cruzi
Título según SCOPUS: New aryloxy-quinone derivatives with promising activity on Trypanosoma cruzi
Título de la Revista: ARCHIV DER PHARMAZIE
Volumen: 353
Número: 1
Editorial: WILEY-V C H VERLAG GMBH
Fecha de publicación: 2020
Idioma: English
DOI:

10.1002/ardp.201900213

Notas: ISI, SCOPUS