Chemical diversity of zoantharians from the coast of Ecuador in the tropical eastern Pacific

This thesis describes the isolation and identification of marine natural products from five zoantharian species collected off the Marine Protected Area El Pelado located in Santa Elena, Ecuador. Ecuador is one of the countries with the greatest terrestrial and marine diversity in the world and relatively few studies have been performed in the marine ecosystem. The Galapagos Island has been considered a “hot spot” of biodiversity and most of these studies have been undertaken in the Archipelago. In 2015, a National Project entitled “Characterization of the biodiversity of microorganisms and invertebrates from the Marine Protected Area El Pelado at the taxonomic, metabolomic and metagenomic level, and their applications for animal and human health” was funded by the Secretary of Higher Education, Science and Technology (SENESCYT) with the aim of describing the existing marine biological and chemical diversity. Therefore, the first inspection of the biodiversity in the Marine Protected Area “El Pelado” (REMAPE) was focused on marine invertebrates. Among the invertebrates observed in this area, zoantharians were one of the most representative organisms with eight species belonging to four families; Zoanthus cf. sociatus, and Zoanthus cf. pulchellus from the family Zoanthidae, Terrazoanthus patagonichus, Terrazoanthus cf. patagonichus and Terrazoantus sp. from the family Hydrozoanthidae, Parazoanthus darwini and Antipathozoanthus hickmani from the family Parazoanthidae and Palythoa cf. mutuki belonging to the family Sphenopidae. Two species of the Parazoanthidae family; P. darwini and A. hickmani seems to be endemic of this ecoregion as there are no reports of the presence of these zoantharians in other marine ecosystems. Interestingly, no chemical studies have been reported from any of these species inhabiting the Ecuadorian coast including the Galapagos Islands. Therefore, this thesis was aimed to study for the first time the chemical diversity of: Terrazoanthus patagonichus (formerly known as T. onoi), Antipathozoanthus hickmani, Parazoanthus darwini, Zoanthus cf. pulchellus and Terrazoanthus cf. patagonichus. A new family of 2-aminoimidazole alkaloids named terrazoanthines A-C were identified from Terrazoanthus patagonichus. Terrazoanthines A and B are characterized by the presence of the 2aminoimidazole ring fused to a cyclohexane. Additionally, two zoanthoxanthin derivatives named zoamides E and F were isolated from the sister species Terrazoanthus cf. patagonichus. Then, four ecdysteroids derivatives named ecdysonelactones were obtained from Antipathozoanthus hickmani. These compounds feature a γ-lactone ring fused to ring A of the ecdysteroid skeleton. Further investigations on this organism led to the identification of four halogenated tyrosine derivatives named valdiviamides A-D and characterized by the presence of iodine and bromine atoms in the phenol ring. The bioactivity study revealed valdiviamide B to have moderate activity against the liver cancer cell line (HepG2) with an IC50 value of 7.8 μM. Additionally, two halogenated tyramine derivatives containing iodine and bromine atoms were identified from Parazoanthus darwini. The chemical investigation of Zoanthus cf. pulchellus allowed the identification of two members of the bioactive family of zoanthamine alkaloids. These compounds revealed anti-inflammatory activity in microglia BV-2 cells used in neuroinflammatory studies with high inhibitory effects in reactive oxygen species (ROS) and nitric oxide (NO) generation. Overall, the chemical studies of these zoantharians led to the identification of 24 secondary metabolites, from which 17 are new natural products. The presented results confirm this overlooked group of invertebrates as a rich source of diverse natural products with unique skeletons and diverse biological activities.