Guanidine alkaloids from marine sponges

Over the past 70 years, marine biodiversity has been recognised as a rich source of unique chemical compounds with wide-ranging applications in the blue bioeconomy. Among marine organisms, sponges have historically been a key focus of marine biodiscovery due to their high potential for yielding novel compounds. More recently, attention has also turned to their associated microbiota-including bacteria, fungi, and cyanobacteria-which have emerged as more sustainable sources of bioactive metabolites. Despite this shift, the marine biodiscovery pipeline continues to feature a significant number of unique metabolites derived from sponges. One notable class of compounds is guanidine alkaloids, which are relatively rare in terrestrial organisms but widely diverse in marine sponges. These can be broadly categorised into two main groups: basic guanidine alkaloids and 2-aminoimidazole alkaloids. In this review, we examine the chemical diversity of sponge-derived guanidine alkaloids reported in the literature since the beginning of marine biodiscovery in the 1950s. This analysis reveals shared metabolic characteristics across different guanidine alkaloid groups, organised according to sponge taxonomic orders, and underscores their remarkable potential as sources of novel marine drugs. Although current research increasingly focuses on marine microbiota, sponges-as complex holobionts-continue to represent an exceptional reservoir of chemical diversity. A deeper functional understanding of the interactions between sponge hosts and their microbial symbionts is likely to play a critical role in translating this rich chemical arsenal into new marine therapeutics in the near future.