Studies on the antifungal and serotonin receptor agonist activities of the secondary metabolites from piezotolerant deep-sea fungus <i>Ascotricha</i> sp.

The potent antifungal agent sesquiterpenes and serotonin 5-HT_2C agonist ascotricin were produced by a newly isolated deep-sea fungus <i>Ascotricha</i> sp. This fungus was isolated from deep-sea sediment collected at a depth of 1235 m and characterized. Piezotolerance was successfully tested under high pressure-low temperature (100 bar pressure and 20ºC) microbial cultivation system. Production of secondary metabolites was enhanced at optimized culture conditions. The <i>in-vivo</i> antifungal activity of sesquiterpenes was studied using the <i>Caenorhabditis elegans – Candida albicans</i> model system. The sesquiterpenes affected the virulence of <i>C. albicans</i> and prolonged the life of the host <i>C. elegans</i>. These findings suggest that sesquiterpenes are attractive antifungal drug candidates. The 5-HT_2C receptor agonist is a potential target for the development of drugs for a range of central nervous system disorders. The interaction of 5-HT_2C agonist ascotricin with the receptor was studied through bioinformatic analysis. The <i>in silico</i> molecular docking and molecular dynamic simulation studies demonstrated that they fit into the serotonin 5-HT_2C active site and the crucial amino acid residues involved in the interactions were identified. To our knowledge, this is first report of <i>in vivo</i> antifungal analysis of sesquiterpenes and <i>in silico</i> studies of serotonin 5-HT_2C receptor-ascotricin complex. MD simulation of interaction of ascotricin with 5-HT2C receptor