Antiviral and antibacterial secondary metabolites from Thai invertebrateassociated fungi

The aim of this thesis is to investigate the secondary metabolites obtained from diverse invertebrate-associated fungi, with the main goal of exploring their bioactivity and structural diversity. This investigation includes studying three different Thai species from the ascomycete order Hypocreales: Cordyceps javanica, and two recently described species, Beauveria neobassiana and Samsoniella aurantia. In a preliminary medium-throughput screening, the total extracts from the above-mentioned strains exhibited promising antiviral properties against the Chikungunya virus (CHIKV) and were selected for the characterization of their secondary metabolites.From the different evaluated media, the cultivation of C. javanica in glucose glycerol (GG1), B. neobassiana in yeast malt extract (YM), and S. aurantia in rice solid medium had positive impacts on the production of diverse secondary metabolites. After preparative purification of the total extracts obtained from the scaled-up cultivation in the aforementioned media, a total of eight compounds (1-8) were isolated from C. javanica, four of which (1,3,6,8) were previously undescribed. From B. neobassiana, seven compounds (9-15) were isolated and elucidated, whereas six compounds (16-21) were obtained and identified from S. aurantia with three previously undescribed compounds from the total extracts of both strains. Extensive analysis, including liquid chromatography-mass spectrometry (LC-MS), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, helped identify these compounds. The obtained results revealed that C. javanica produced a class of cyclodepsipeptides trivially named beauverolides (1-8). In parallel, the metabolomics analyses highlighted the structural diversity of thesemetabolites. Moreover, they played a key role in confirming structural hypotheses and exploring non-isolated compounds. Beauveria neobassiana produced several polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS)-derived metabolites, including vancouverone C (9), pyridovericin (10), 15-OH-tenellin (11), prototenellin D (12), vancouverone D (13), pretenellin B (14) and tenellin (15). Notably, prototenellin D (12) emerged as a promising anti-biofilm agent against Staphylococcus aureus biofilms, characterized by the absence of antimicrobial activity and low cytotoxicity against the tested microorganisms and cell lines, respectively. Similarly, tenellin (15) showed notable potential against Bacillus subtilis.