Pyridinium alkaloids – a unique class of naturally occurring salt-form secondary metabolites: a comprehensive review of 68 years (1958–mid-2025)

Pyridinium alkaloids represent a structurally unique class of nitrogen-containing natural products, primarily obtained from marine sponges. These compounds range from simple mono-substituted derivatives to complex poly-alkylated and a series of unusual oligomeric structures. Additionally, they have also exhibited a wide range of documented biological activities, including cytotoxic, antimicrobial, antifungal, and neuroactive effects. Notably, several compounds, such as coscinoderines and cyclostellettamines, have been explored for their ability to exhibit selective cytotoxicity against nutrient-deprived cancer cells. Polyalkylpyridiniums also represent a promising avenue for drug development due to their potent and diverse biological activities. This is especially the case for halitoxin, a polymeric complex from sponges, which shows high cytotoxicity and strong antibacterial activity, as well as the ability to prevent the onslaught of marine organisms. This review aims to provide a comprehensive overview of 127 pyridinium alkaloid derivatives published in a ranging of 68 years from 1958 to mid-2025, highlighting their sources, structural classes, bioactivities, biosynthetic origins, and synthetic insights. Subsequent assessments and discussions will provide a foundation for further research and development on potential compounds of this class.