The microbial transformation of cyclocanthogenol (CCG), Astragalus sp. originated sapogenin, by the endophytic fungus Alternaria eureka 1E1BL1 isolated from Astragalus angustifolius was investigated. Hydroxylation, oxidation, epoxidation, O-methylation, ring-expansion and methyl migration reactions were observed on the triterpenoid skeleton. As a result, eight metabolites were isolated and the structures of the previously undescribed compounds were established by 1-D, 2-D NMR and HR-MS analyses.

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The xylariaceous genus Dematophora has recently been resurrected and segregated from Rosellinia based on a molecular phylogeny and morphological characters. This was an important taxonomic change because Dematophora in the current sense contains several important pathogens, while Rosellinia is limited to mainly saprotrophic species that have an endophytic stage in their life cycle and may even have beneficial effects on the host plants. During our ongoing work on the functional biodiversity of the Xylariales, we have encountered new strains of rosellinoid Xylariaceae from Iran and have studied their mycelial cultures for secondary metabolites in an attempt to establish further chemotaxonomic affinities. In the process, we isolated and identified 13 compounds, of which rosellisteroid (1), the cichorine derivative 2, and the alkaloid 3 are new. Out of these, nine were tested for their antimicrobial affinities with cytochalasin E (6) exhibiting weak activity against Schizosaccharomyces pombe. The cytotoxicity of three cytochalasin derivatives was examined and their effects on the F-actin cytoskeletal organization studied by fluorescence microscopy using fluorescent phalloidin. Cytochalasin E (6) and Δ6,12-cytochalasin E (7) showed strong and irreversible action on actin, while cytochalasin K (8) exhibited weaker, reversible effects.

Biotransformation of Astragalus sapogenins (cycloastragenol (1) and astragenol (2)) by Astragalus species originated endophytic fungi resulted in the production of five new metabolites (3,7,10, 12,14) together with 10 known compounds. The structures of the new compounds were established by NMR spectroscopic and HRMS analysis. Oxygenation, oxidation, epoxidation, dehydrogenation, and ring cleavage reactions were observed on the cycloartane (9,19-cyclolanostane) nucleus. The ability of the compounds to increase telomerase activity in neonatal cells was also evaluated. After prescreening studies to define potent telomerase activators, four compounds were selected for subsequent bioassays. These were performed using very low doses ranging from 0.1 to 30 nM compared to the control cells treated with DMSO. The positive control cycloastragenol and 8 were found to be the most active compounds, with 5.2-(2 nM) and 5.1-(0.5 nM) fold activations versus DMSO, respectively. At the lowest dose of 0.1 nM, compounds 4 and 13 provided 3.5and 3.8-fold activations, respectively, while cycloastragenol showed a limited activation (1.5-fold).