UMYMFOR   05516
UNIDAD DE MICROANALISIS Y METODOS FISICOS EN QUIMICA ORGANICA
Unidad Ejecutora - UE
artículos
Título:
Activity of fluorine-containing analogues of WC-9 and structurally related analogues against two intracellular parasites: Trypanosoma cruzi and Toxoplasma gondii
Autor/es:
MARÍA N. CHAO; BRUNO N. FALCONE; ROBERTO DOCAMPO; MARÍA N. CHAO; BRUNO N. FALCONE; ROBERTO DOCAMPO; MELISSA STOREY; SERGIO M. BONESI; JUAN B. RODRIGUEZ; MELISSA STOREY; CATHERINE LI; SERGIO M. BONESI; SERGIO H. SZAJNMAN; JUAN B. RODRIGUEZ; SILVIA N. J. MORENO; CATHERINE LI; SERGIO H. SZAJNMAN; SILVIA N. J. MORENO
Revista:
CHEMMEDCHEM
Editorial:
WILEY-V C H VERLAG GMBH
Referencias:
Lugar: Weinheim; Año: 2016 vol. 11 p. 2690 - 2702
ISSN:
1860-7179
Resumen:
Two obligate intracellular parasites, Trypanosoma cruzi, the agent of Chagas disease, and Toxoplasma gondii, an agent of toxoplasmosis, upregulate the mevalonate pathway of their host cells upon infection, which suggests that this host path- way could be a potential drug target. In this work, a number of compounds structurally related to WC-9 (4-phenoxyphenox- yethyl thiocyanate), a known squalene synthase inhibitor, were designed, synthesized, and evaluated for their effect on T. cruzi and T. gondii growth in tissue culture cells. Two fluorine-con- taining derivatives, the 3-(3-fluorophenoxy)- and 3-(4-fluorophenoxy)phenoxyethyl thiocyanates, exhibited half-maximal ef- fective concentration (EC50) values of 1.6 and 4.9 mm, respec- tively, against tachyzoites of T. gondii, whereas they showed similar potency to WC-9 against intracellular T.cruzi (EC50 values of 5.4 and 5.7mm, respectively). In addition, 2-[3- (phenoxy)phenoxyethylthio]ethyl-1,1-bisphosphonate, which is a hybrid inhibitor containing 3-phenoxyphenoxy and bis- phosphonate groups, has activity against T. gondii proliferation at sub-micromolar levels (EC50 = 0.7 mm), which suggests a com- bined inhibitory effect of the two functional groups.