Structure-Activity relationship studies on a TPR dendrimer with dual activities against HIV and enterovirus A71. Modifications on the amino acid

We have recently described a new class of dendrimers with tryptophan (Trp) on the surface that show dual antiviral activities against HIV and EV71 enterovirus. The prototype compound of this family is a pentaerythritol derivative with 12 Trps on the periphery. Here we complete the structure-activity...

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Detalles Bibliográficos
Autores: Martínez Gualda, Belén V., Sun, Liang, Rivero Buceta, Eva María, Flores Aguilar-Amat, Aída, Quesada Del Sol, Ernesto, Balzarini, Jan, Noppen, Sam, Liekens, Sandra, Schols, Dominique, Neyts, Johan, Leyssen, Pieter, Mirabelli, Carmen, Camarasa Rius, María José, San Félix García, Ana Rosa
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/99617
Acceso en línea:https://hdl.handle.net/20.500.14352/99617
Access Level:acceso abierto
Palabra clave:661.185
615:54
615.31
Antiviral agents
Tryptophan
EV71
HIV
HFMD
AIDS
Ciencias Biomédicas
Química farmaceútica
Química orgánica (Farmacia)
2306 Química Orgánica
2390 Química Farmacéutica
Descripción
Sumario:We have recently described a new class of dendrimers with tryptophan (Trp) on the surface that show dual antiviral activities against HIV and EV71 enterovirus. The prototype compound of this family is a pentaerythritol derivative with 12 Trps on the periphery. Here we complete the structure-activity relationship studies of this family to identify key features that might be significant for the antiviral activity. With this aim, novel dendrimers containing different amino acids (aromatic and non-aromatic), tryptamine (a “decarboxylated” analogue of Trp) and N-methyl Trp on the periphery have been prepared. Dendrimer with N-Methyl Trp was the most active against HIV-1 and HIV-2 while dendrimer with tyrosine was endowed with the most potent antiviral activity against EV71. This tyrosine dendrimer proved to inhibit a large panel of EV71 clinical isolates (belonging to different clusters) in the low nanomolar/high picomolar range. In addition, a new synthetic procedure (convergent approach) has been developed for the synthesis of the prototype and some other dendrimers. This convergent approach proved more efficient (higher yields, easier purification) than the divergent approach previously reported.

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