Masking strategies for the bioorthogonal release of anticancer glycosides

Abstract

Significant progress in the bioorthogonal field has resulted in the advent of a new type of prodrug: bioorthogonal prodrugs, i.e. metabolically stable precursors of therapeutic agents that are specifically activated by non-native, non-biological, non-perturbing physical or chemical stimuli. The application of such unique drug precursors in conjunction with their corresponding activating source is under preclinical experimentation as a novel way to elicit site-specific activation of cytotoxic drugs, with particular emphasis on anticancer glycosides. In this chapter, the strategies developed for the masking and bioorthogonal release of cytotoxic nucleosides using benign electromagnetic radiations, biocompatible click chemistry and bioorthogonal organometallic (BOOM) catalysis will be discussed in detail.