Photo-Amygdalin: Light-dependent control over hydrogen cyanide release and cytotoxicity

Abstract

Amygdalin is a natural glycosidic compound found in bitter almonds and apricot seeds. After enzymatic hydrolysis, amygdalin forms a cyanohydrin which spontaneously decays to release toxic hydrogen cyanide in a process called cyanogenesis. Due to this capacity to release cyanide, it has a long and controversial history of use as anticancer therapeutic in alternative medicine. However, the inability to control amygdalin’s cyanogenesis hinders its efficient medical use and renders it potentially dangerous. In this study we describe the design and development of ‘photo-amygdalin’, a compound whose cyanogenesis can be triggered by visible light. We synthesize photo-amygdalin inspired by the molecular structure of amygdalin, illustrate its capability to form hydrogen cyanide upon irradiation through a myoglobin test, and showcase its ability to significantly reduce the viability of a human cell line upon irradiation, proving to be 100-fold more potent than potassium cyanide.