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

•Novel dendrimers containing different amino acids on the periphery have been synthesized.•These compounds have dual action against HIV and EV71.•Tyrosine dendrimer is the most potent against EV71 while dendrimer with N-methyl Trp is the most potent against HIV-1.•Dendrimer with tyrosine is an extremely highly potent inhibitor of clinical EV71 isolates (nanoMolar-picoMolar potency).•Presence of hydrophilic groups (NH, OH) on the aromatic ring of the amino acid is beneficial for anti-EV71 activity.

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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