Abstract
Isoquinoline alkaloids are an important class of natural products with diverse chemical structures and promising pharmacological activities, attracting widespread attention from researchers. This review summarizes the latest literature related to isoquinoline alkaloids from 2019 to 2023, focusing mainly on their biological activities and mechanisms of action as a continuation and update of our previous review. During this period, a large number of novel isoquinoline alkaloids were isolated, discovered, and deeply studied. Among them, 79 compounds, as well as several previously known compounds, have a wide range of bioactivities, including antitumor, antibacterial, anti-inflammatory, antiparasitic, insecticidal, neuroprotective, cardioprotective, and analgesic activities, as well as effects on bone diseases and on diabetes and its complications. The underlying mechanisms of action of some famous alkaloids (berberine, sanguinarine, etc.) have been studied systemically using modern techniques. In addition, a series of active natural product derivatives have been constructed easily and efficiently by an optimization strategy for the direct modification of active natural products, and some derivatives with better activity and safety have been obtained, providing new indications or opportunities for the discovery of novel drug molecules. In the long term, research on the identification of isoquinoline alkaloids and the exploration of new bioactivities and novel modes of action will pave the way for targeted pharmacological production in industry, and the development of new isoquinoline derivatives will provide important support for the search for new and better drugs. • The chemical structures of new isolated isoquinoline alkaloids are elucidated. • The bioactivities of new isolated and known isoquinoline alkaloids are highlighted. • The potential mechanism of action of isoquinoline alkaloids are critical discussed. • Isoquinoline derivatives as well as the optimization strategy are demonstrated.