Design, synthesis and biological evaluation of enzymatically cleavable NSAIDs prodrugs derived from self-immolative dendritic scaffolds for the treatment of inflammatory diseases

In this paper, three different dendritic scaffords of enzymatically cleavable naproxen conjugates have been synthesized in a convergent approach and well characterized by NMR and MS techniques. The efficient release of the active drug moiety occurred by the cleavage of different benzyl ester or amide triggers by enzymatic activation of hydrophobic self-immolative dendritic prodrugs, cleavage properties and cytotoxicity of the new conjugates are also presented. Moreover, all prodrugs were also found to possess more significant anti-inflammatory activity and less degree of ulcerogenic potential in vivo than their monomeric counterpart naproxen.