Pharmacognosy and natural product chemistry of the marine sponge Hyrtios erectus

Marine-derived bioactive natural products are an essential resource for drug discovery. In particular, marine sponges and associated symbionts can be exploited to discover innovative compounds and new drug candidates. The sponge Hyrtios erectus which is largely distributed in Asian tropical areas, has been extensively investigated as a source of bioactive natural products. A detailed analysis of the natural products isolated from this sponge and their pharmacological properties has been performed. The study led to the identification of over 160 natural products, including over 50 alkaloids, 100 terpenoids and a few other compounds like phenolic alkenes (erectuseneols), chromanones (hyrtiosones) and cyclic peptides (spongitatin-1). The survey introduces multiple series of products, such as the hyrtiosins, hyrtiosulawesine, hyrtiazepine, hyrtioerectines, hyrtioreticulins, hyrtimomines, hyrtinadines, and hainanerectamines among the alkaloids. A large range of sesterterpenes and sesquiterpenes have been isolated, in particular scalarane-type sesterterpenoids such as erectascalaranes A-B, hyrtioscalaranes A-B and hyrtiosins A-F, in addition to a panoply of scalarin and scalaradial derivatives. All these compounds are presented together with their pharmacological properties. Synthetic procedures leading to some of these natural products and analogues are described, notably for hyrtiozulawesine, hyrtinadine A, hytiosine B, and salmahyrtisol A. At the pharmacological level, the most interesting products and associated molecular targets are discussed, such as the targeting of the orphan nuclear receptor Nur77 with 12- epi -scalaradial derivatives. An updated view of the chemical and pharmacological diversity associated with Hyrtios erectus is provided with the goal to promote further researches with this sponge erected as an emblematic figure of the marine natural product chemistry. • About 170 bioactive natural products have been isolated from the sponge Hyrtios erectus. • Over 50 alkaloids have been characterized, with synthetic routes described. • A hundred terpenoids have been reported, notably scalarane sesterterpenoids. • The pharmacological properties of the products are detailed. • An overview of the chemical content of the sponge is presented.