INVESTIGADORES
TRIPODI Karina Eva Josefina
artículos
Título:
Synergistic effect of inhibitors of fatty acid desaturases on Trypanosoma parasites
Autor/es:
ALLOATTI, ANDRÉS; TRIPODI, KARINA; UTTARO, A. D.
Revista:
PARASITOLOGY RESEARCH
Editorial:
SPRINGER
Referencias:
Lugar: Berlin; Año: 2013
ISSN:
0932-0113
Resumen:
Abstract The pathway for unsaturated fatty acid biosynthesis
is essential in trypanosomatid parasites and has been a
key target in our work on the discovery and analysis of
several inhibitory compounds. Here, we show the effect of
novel inhibitors of stearoyl-CoA desaturase (SCD) and
oleate desaturase (OD), alone and in combination, on the
growth rate of parasite cultures. GS-456332, an inhibitor of
human Δ9 desaturase, efficiently inhibited growth of both
Trypanosoma cruzi epimastigotes and Trypanosoma brucei
bloodstream form cells, with EC50 values of 136.9±24.2 and
9.4±3.1 nM, respectively. This effect was specific for SCD.
Stearolic acid (9-octadecynoic acid) was also able to arrest T.
cruzi and T. brucei growth by specific inhibition of their OD,
with EC50 values of 1.0±0.2 μM and 0.1±0.01 μM, respectively.
When these compounds were administered simultaneously,
a clearly synergistic effect was observed for both
Trypanosoma species, with EC50 values in the low nanomolar
range. These results demonstrate the feasibility of using combinations
of drugs, inhibiting different enzymes on the same
metabolic pathway, for the development of more efficient
chemotherapeutic strategies against neglected diseases caused
by these parasites.