Antibacterial phenylspirodrimanes from the marine-derived fungus Stachybotrys sp. SCSIO 40434.

Five new phenylspirodrimanes, stachybomycins A - E (1-5), together with four known compounds (6-9), were isolated from the marine-derived fungus Stachybotrys sp. SCSIO 40434. Their structures were elucidated by comprehensive spectroscopic analyses of NMR and HRESIMS. The absolute configuration of 1 was confirmed by single crystal X-ray diffraction analysis. Compounds 5 and 7 showed moderate antibacterial activities against Micrococcus luteus, Staphylococcus aureus and methicillin resistant Staphylococcus aureus with minimal inhibition concentration (MIC) values of 8, 16 and 16 µg mL-1, respectively.

Atranones from Stachybotrys chartarum and their antitumor activities in MG-63 human osteosarcoma cells.

Two new atranones T and U (1 and 2), and three known analogues atranone B (3), atranone Q (4), and stachatranone C (5) were isolated from the toxigenic fungus Stachybotrys chartarum. Their structures and absolute configurations were elucidated by spectroscopic data and calculated ECD analyses. The cytotoxicities of all the atranones (1-5) were evaluated against MG-63 human osteosarcoma cell lines. Compound 4 exhibited significant cytotoxic effect against MG-63 with IC50 value of 8.6 µM, being more active than the positive control, 5-FU (IC50 10.4 µM). Morphological features of apoptosis activities were evaluated in 4-treated MG-63 cells. Compound 4 effectively induced apoptosis of MG-63, which was associated with G0/G1-phase cell cycle arrest. Flow cytometric analysis showed that the treatment by 4 significantly induced MG-63 cell apoptosis in a dose-dependent manner.

Bistachybotrysins F-J, five new phenylspirodrimane dimers with a central cyclopentanone linkage from Stachybotrys chartarum.

Bistachybotrysins F-J (1-5), five new phenylspirodrimane dimers with a central cyclopentanone core were isolated from Stachybotrys chartarum CGMCC 3.5365. The structures of 1-5 were elucidated through extensive spectroscopic data analysis, including 1D/2D NMR, HR-MS, and ECD spectra. Compounds 3-5 displayed moderate cytotoxic activity against the cell lines HCT116, NCI-H460, and HepG2 with IC50 values ranging from 9.1 to 12.2 µM, making them promising as lead compounds for drug research and discovery.

A new phenylspirodrimane dimer from the fungus Stachybotrys chartarum.

A new phenylspirodrimane dimer, named stachartarin A (1), was isolated from cultures of the tin mine tailings-associated fungus Stachybotrys chartarum. Its structures were elucidated by means of spectroscopic methods. At the same time, the compound was tested for its cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cells.

Novel Isochroman Dimers from Stachybotrys sp. PH30583: Fermentation, Isolation, Structural Elucidation and Biological Activities.

The rare anishidiol and five new isochromans, including three novel dimers with unprecedented skeletons, were isolated from Stachybotrys sp. PH30583. Their structures were determined by spectral analyses. The bioactivities of these compounds were also investigated. The dimers (6-10) inhibited acetylcholinesterase at 50 µM, but the monomers did not. To investigate the biogenesis of the novel dimers, a time-course investigation of metabolite production was undertaken.

Stachybisbins A and B, the first cases of seco-bisabosquals from Stachybotrys bisbyi.

Stachybisbins A (1) and B (2), two new meroterpenoids with unprecedented seco-bisabosqual skeleton, together with three biogenetically related metabolites (3-5), were isolated from a wetland fungal strain of Stachybotrys bisbyi. The structures of the new compounds were determined by spectroscopic analyses, modified Mosher's method, and quantum chemical CD method. The cytotoxic activities of all compounds were tested against HL-60, SMMC-7721, A-549, MCF-7, and SW480 human cancer cell lines.

SMTP-7, a novel small-molecule thrombolytic for ischemic stroke: a study in rodents and primates.

SMTP-7 (Stachybotrys microspora triprenyl phenol-7), a small molecule that promotes plasminogen activation through the modulation of plasminogen conformation, has excellent therapeutic activity against cerebral infarction in several rodent models. Detailed evaluations of SMTP-7 in a primate stroke model are needed for effective, safe drug development. Here we evaluated SMTP-7 in a monkey photochemical-induced thrombotic middle cerebral artery (MCA) occlusion model (n=6), in which MCA occlusion was followed by recanalization/reocclusion. SMTP-7 (10 mg/kg, intravenous infusion) significantly increased the postinfusion MCA recanalization rate (32.5-fold, P=0.043) and ameliorated the post-24-h neurologic deficit (by 29%, P=0.02), cerebral infarct (by 46%, P=0.033), and cerebral hemorrhage (by 51%, P=0.013) compared with the vehicle control animals. In normal monkeys, SMTP-7 did not affect general physiologic or hemostatic variables, including coagulation and platelet parameters. Investigations in rodent models of transient and permanent focal cerebral ischemia, as well as arterial thrombosis and bleeding tests, suggest a role for SMTP-7's regulated profibrinolytic action and neuroprotective properties in the monkey MCA occlusion model. In conclusion, SMTP-7 is effective in treating thrombotic stroke in monkeys. SMTP-7 is thus a promising candidate for the development of alternative therapy for ischemic stroke.

Selective production of staplabin and SMTPs in cultures of Stachybotrys microspora fed with precursor amines.

Staplabin and SMTPs, a family of triprenyl phenol metabolites of Stachybotrys microspora, enhance fibrinolysis by modulating plasminogen conformation to increase its susceptibility to activation by plasminogen activators. We found that the production of these metabolites were markedly elevated by feeding the microbial culture with an amino acid or an amino alcohol that is a partial molecular constituent of the compound. Thus, the addition of 5-aminovaleric acid, 2-aminoethanol, Ser, Phe, Leu, Trp, Orn and Lys at 100 mg/ml resulted in 7- to 45-fold increases in the production of staplabin, SMTP-1, -3, -4, -5, -6, -7 and -8, respectively. Although the feeding at day 0 to 3 of culture supported the selective production, the supplementation after 5 days had little or no effect. When non-constituent amino acids were supplemented to cultures, production of hitherto uncharacterized congeners was observed.