Stizophyllin

Pregnane-type steroids from the inedible mushroom Thelephora terrestris.[Pubmed:15744104]

Chem Pharm Bull (Tokyo). 2005 Mar;53(3):309-12.

Chromatographic fractionation of the methanol extract of fruiting bodies of the inedible Japanese mushroom Thelephora terrestris (Thelephoraceae) has led to the isolation and characterization of two unusual new pregnane-type steroids, 2beta,3alpha-dihydroxypregna-4,7,16-trien-12,20-dione (2) and 1alpha,2beta,3alpha-trihydroxypregna-4,7,16-trien-12,20-dione (3) named terresterones A and B (2, 3), as well as the previously known compound Stizophyllin, now assigned as 2beta,3alpha,12beta-trihydroxypregna-4,7,16-trien-20-one (1). Elucidation of their structures and the revision of the stereochemical assignment of Stizophyllin were achieved by means of extensive 1D and 2D NMR, UV, CD, IR, MS and molecular modeling experiments. This paper presents the first report on the isolation of true pregnane-type steroids from the Fungi kingdom.

Cell-cycle specific cytotoxicity mediated by stizophyllin (2 alpha,3 beta,12 beta-trihydroxypregna-4,7,16-trien-20-one), a novel electrophilic pregnane isolated from Stizophyllum riparium.[Pubmed:1913978]

Chem Biol Interact. 1991;80(1):43-56.

A structurally-novel pregnane derivative, 2 alpha,3 beta,12 beta-trihydroxypregna-4,7,16-trien-20-one (Stizophyllin), was isolated from an extract of Stizophyllum riparium (H.B.K.) Sandw. on the basis of bioactivity-guided fractionation and confirmed to mediate a potent cytotoxic response with cultured P-388 cells. We presently report a detailed isolation procedure and the results of studies designed to examine its mechanism of action. By means of a Michael-type addition, Stizophyllin formed adducts with nucleophilic substances such as L-cysteine and beta-mercaptoethanol. The adduct with beta-mercaptoethanol was isolated, structurally characterized, and found to be 20-fold less cytotoxic than Stizophyllin. Stizophyllin interacted with DNA, but no mutagenicity was observed with Salmonella typhimurium strain TM677 or cultured Chinese hamster ovary cells, and no in vitro reaction occurred with guanosine. Relative to control cell cultures, the total biosynthesis of DNA, RNA or protein was reduced when P-388 cells were treated with Stizophyllin. However, the cell number did not increase in the presence of inhibitory Stizophyllin concentrations (e.g., 4 micrograms/ml), and the DNA content (per cell) actually doubled after approximately 48 h. Consistent with this, Stizophyllin blocked the cells in the G2 + M compartment of the cycle, and the block appeared to be specific for the G2 phase. Accordingly, Stizophyllin did not modulate in vitro tubulin polymerization reactions nor did it affect the morphology of dibutyryl cAMP-treated astrocytoma cells in culture. These data suggest that the cytotoxic activity of Stizophyllin is mediated by covalent reaction with a cellular component (such as a sulfhydryl-containing protein) by means of a Michael-type addition. Based on the cell-cycle specificity of the response, it appears that this interaction prevents the cells from progressing through mitosis.

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