An update on the toxicity of cyanogenic glycosides bioactive compounds: Possible clinical application in targeted cancer therapy

Cyanogenic glycosides are defined as natural herbal toxins which are found in more than 2000 plant species and most of them consumed by humans. These nitrile-containing compounds do not present toxic effects in intact form while they produce toxic cyanide following enzymatic digestion. Therefore, over-consuming of these compounds can lead to cyanide poisoning. On the other hand, some cyanogenic compounds such as amygdalin and linamarin have therapeutic effects and they have been used as a traditional medicine to treat several diseases such as cancer. It seems that the biological properties of these compounds such as bioavailability, solubility, and stability elevate by glycosylation which causes the increased anti-tumor activity of compounds. However, a major challenge in its various applications such as anti-cancer drugs is cyanide poisoning which has been reported in some patients. Interestingly, different approaches of targeted therapy have been applied to elevate these compounds' pharmaceutical properties in targeting cancer cells, like suicide gene therapy, antibody-directed enzyme prodrug therapy (ADEPT), and nanoporous imprinted polymers (nanoMIPs). In this review, we have focused on the challenges of cyanide toxicity raised from amygdalin and linamarin and on various approaches to their targeted therapy in cancer treatment as well.