IQUIR   05412
INSTITUTO DE QUIMICA ROSARIO
Unidad Ejecutora - UE
artículos
Título:
New synthetic anti-infective agents by scaffold prenylation
Autor/es:
GUILLERMO R. LABADIE; EXEQUIEL O.J. PORTA; SEBASTIÁN JÄGER ; LUCIA FARGNOLI
Revista:
CHEMICKé LISTY
Editorial:
CHEMICKE LISTY
Referencias:
Lugar: Praga; Año: 2014 vol. 108 p. 1092 - 1094
ISSN:
0009-2770
Resumen:
NEW SYNTHETIC ANTI-INFECTIVE AGENTS BY SCAFFOLD PRENYLATION GUILLERMO R. LABADIE*, EXEQUIEL O. J. PORTA,SEBASTIÁN JÄGER, LUCIA FARGNOLI. Instituto de Química Rosario (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario. Suipacha 531, Rosario (2000), Argentina labadie@iquir-conicet.gov.ar World most vulnerable population is in risk of being affected by Neglected Tropical Diseases (NTD). One out of seven people around the globe is affection by those diseases theforecast is not going to change in the near future. The arsenal of present treatments are insufficient and inefficient leading to urgent need of new drugs and strategies to prevention. Within the universe of small organic molecules, the isoprenoids are the most important and numerous families of metabolites. It has been proposed that prenylated products are more potent than their unsubstituted counterpart. Based on those concepts and as a part of an ongoing program to develop new drugs against NTD, we wanted to explore the scaffold prenylation as a novel strategy to find new chemical entities. The implemented strategy requires the selection of adequate scaffold that were conveniently prenylated. The selected reaction for the scaffold decoration included the direct scaffold N, O or C alkylation and Copper(I)-catalyzed AzideAlkyne Cycloaddition (CuAAC)3 of previously functionalized clickable substrate . The generated libraries were screened against ethiological agents of malaria (P. falciparum chloroquine sensitive and resistant strains), visceral leishmaniasis (L. donovani), HAT (T. brucei) and Chagas´ disease (T. cruzi). As result of our effort we have found very promising new hits to develop drugs against trypanosomiasis, malaria and other diseases. This investigation received financial support from the WHOTDR, CONICET, Josefina Prats Foundation and National Agency for Science and Technology of Argentina. REFERENCES 1. Yamey G., Hotez P.: BMJ 335, 269 (2007). 2. Botta B., Delle Monache G., Menendez P., Boffi A.:Trends. Pharmacol. Sci. 26, 606 (2005). 3. Thirumurugan P., Matosiuk D., Jozwiak K.: Chem. Rev.113, 4905 (2013).