pseurotin and synerazol

A natural product, pseurotin A inhibits IgE production in vitro. Wide variety of chemical modification of pseurotin A was performed. Structure-activity relationship studies of pseurotin analogues elucidated that 10-deoxypseurotin A strongly inhibits IgE production with IC(50) of 0.066 microM. An immunosuppressive activity of another natural product, synerazol was also found.

Topics: Animals; Immunoglobulin E; Immunosuppressive Agents; Mice; Mice, Inbred BALB C; Pyrrolidinones; Structure-Activity Relationship

Two natural products, synerazol and pseurotin E, were synthesized from the natural product pseurotin A in 58% and 57% yields, respectively in one-pot procedures. This work also establishes the absolute stereochemistry of pseurotin E.

Topics: 4-Butyrolactone; Molecular Structure; Pyrrolidinones; Stereoisomerism

Aspergillus fumigatus TP-F0196 produces pseurotin A, synerazol and gliotoxin. Phenylalanine is a common biosynthetic precursor of these antibiotics. Feeding fluorophenylalanine to the culture induced the production of novel fluorinated analogs. These fluorinated antibiotics were obtained from the culture broth by solvent extraction and purified by chromatographies, and their antimicrobial and antitumor activities were investigated. Among the novel fluorinated analogs, 19- and 20-fluorosynerazols exhibited potent anti-angiogenic activity in the chorioallantoic membrane assay. In addition, 19-fluorosynerazol showed more potent cytocidal activity against several cancer cell lines than synerazol.

Topics: Angiogenesis Inhibitors; Antifungal Agents; Aspergillus fumigatus; Bacteria; Cell Line, Tumor; Chromatography, High Pressure Liquid; Drug Screening Assays, Antitumor; Fermentation; Fluorides; Gliotoxin; Humans; Immunosuppressive Agents; Magnetic Resonance Spectroscopy; Mass Spectrometry; Microbial Sensitivity Tests; Pyrrolidinones