Chemistry and biological activities of hetisine-type diterpenoid alkaloids

Hetisine-type C(20)-diterpenoid alkaloids (DAs) are one of the most important DA subtypes. During the past decades, a total of 157 hetisine-type DAs were obtained from plants from seven genera in three families, most of which were isolated from the genera Aconitum and Delphinium in the Ranunculaceae family. Structurally, hetisine-type DAs are characterized by a heptacyclic hetisane skeleton formed by the linkage of C(14)–C(20) and N–C(6) bonds in an atisine-type DA, and their structural diversity is created by the states of the N atom and various substituents. Pharmacological studies have revealed a wide range of pharmacological actions for hetisine-type DAs, including antiarrhythmic, antitumor, antimicrobial and insecticidal activities, as well as effects on peripheral vasculature, which are closely related to their chemical structures. In particular, the prominent antiarrhythmic effects and low toxicity of hetisine-type DAs highlight their potential in antiarrhythmic drug discovery. Hetisine-type DAs with diverse bioactivities are promising lead structures for further development as commercial agents in medicine.