Photoactivatable prodrugs

Photoresponsive molecules are versatile tools used in photopharmacology for the activation of drugs with light irradiation, thus potentially enabling spatiotemporal control over their potency. Photocleavable protecting groups (PPGs), which are small molecules covalently bound to a bioactive compound to block its therapeutic action, represent cornerstone tools within this research area. Irradiating a PPG-based prodrug induces the cleavage of its bond with the bioactive compound (drug), which is released restoring its biological activity. Although several issues need to be addressed for their clinical application, photoactivatable prodrugs represent an attractive research field to develop novel therapeutic tools. This chapter focuses on the main classes of PPGs for biological applications. The “ideal” properties of PPG-based prodrugs and the mechanistic aspects of reactions underlying the light activation of photoactivatable prodrugs are discussed. An overview on advances in the field, with particular emphasis on selected recently reported examples of drugs photorelease, as well as challenges ahead, is provided.