Artículo
Design, Synthesis and Biological Activity of C3 Hemisynthetic Triterpenic Esters as Novel Antitrypanosomal Hits
Schioppa, Laura; Beaufay, Claire; Bonneau, Natacha; Sánchez, Marianela
; Girardi, Cynthia Natalia; Leverrier, Aurélie
; Ortiz, Sergio; Palermo, Jorge Alejandro
; Poupaert, Jacques H.; Quetin Leclercq, Joelle
Fecha de publicación:
09/2021
Editorial:
John Wiley & Sons Inc
Revista:
ChemistryOpen
ISSN:
2191-1363
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Research for innovative drugs is crucial to contribute to parasitic infections control and eradication. Inspired by natural antiprotozoal triterpenes, a library of 12 hemisynthetic 3-O-arylalkyl esters was derived from ursolic and oleanolic acids through one-step synthesis. Compounds were tested on Trypanosoma, Leishmania and the WI38 cell line alongside with a set of triterpenic acids. Results showed that the triterpenic C3 esterification keeps the antitrypanosomal activity (IC50≈1.6–5.5 μm) while reducing the cytotoxicity compared to parent acids. Unsaturation of the ester alkyl chain leads to an activity loss interestingly kept when a sterically hindered group replaces the double bond or shields the ester group. An ursane/oleanane C3 hydroxylation was the only important feature for antileishmanial activity. Two candidates, dihydrocinnamoyl and 2-fluorophenylpropionyl ursolic acids, were tested on an acute mouse model of African trypanosomiasis with significant parasitemia reduction at day 5 post-infection for the dihydrocinnamoyl derivative. Further evaluation on other alkyl/protective groups should be investigated both in vitro and in vivo.
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(CCT - CORDOBA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - CORDOBA
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - CORDOBA
Citación
Schioppa, Laura; Beaufay, Claire; Bonneau, Natacha; Sánchez, Marianela; Girardi, Cynthia Natalia; et al.; Design, Synthesis and Biological Activity of C3 Hemisynthetic Triterpenic Esters as Novel Antitrypanosomal Hits; John Wiley & Sons Inc; ChemistryOpen; 10; 9; 9-2021; 896-903
Compartir
Altmétricas