Irelands’ hidden pharmacy: Marine biodiscovery applied to deep-sea sponges and corals

• Main Author: Afoullouss, Sam
• Other Authors: Thomas, Olivier, Science Foundation Ireland
• Format: Thesis
• Language: unknown
• Published: NUI Galway 2022
• Subjects: deep sea; Drug discovery; corals; natural product chemistry; sponges; Science and Engineering; Science; Chemistry; Paragorgia arborea
• Online Access: http://hdl.handle.net/10379/17341

Natural products have provided over 60% of our medicines to date, but their search has focused on easy to access habitats, leaving the marine realm underexplored. The deep-sea, which is the world’s largest biome and contains some of the most biodiverse and inaccessible ecosystems, could represent an untapped source of natural products, especially since harsh environmental gradients and competition for resources in deep-sea habitats can lead to evolutionary adaptations with the potential to yield novel internal chemistry. A series of three expeditions to Ireland’s continental slope and associated submarine canyon systems, collected corals and sponges from rich habitats. As part of a wider project whose aim was to isolate novel bioactive deep-sea metabolites with pharmaceutical potential, herein focus was applied to two species. Characella pachastrelloides was selected because of the interesting chemical profile of an initial extract. Paragorgia arborea was selected for its bioactivity in a screening programme. Four novel glycolipopeptides which contain a rare sugar moiety and rare D-amino acids were extracted and elucidated from the deep-sea sponge Characella pachastrelloides collected in Whittard Canyon at 800 m depth. These four compounds represent two pairs of stereo enantiomers which differ in the length of the fatty acid chain. Enantiomers Characellide A and B showed potent anti-inflammatory activity in a bioassay measuring ROS production. Subsequent synthesis of Characellide A by international colleagues demonstrated that further analysis of the absolute configuration of the natural product is required. It became apparent that optimisation of classical and feature-based data acquisition parameters was required to effectively apply molecular networking to fractions of the Characella pachastrelloides extract. A fractional factorial analysis applied to three extracts (an alga, a sea squirt and a zoanthid) that varied widely in their chemodiversity showed that four factors have the greatest effect on molecular ...