benzofurans and bisdechlorogeodin

Two new polyketide natural products, globosuxanthone F (

Topics: Animals; Antineoplastic Agents; Ascomycota; Benzofurans; Cell Line, Tumor; Dose-Response Relationship, Drug; Humans; Inhibitory Concentration 50; Leukemia, T-Cell; Molecular Structure; Polyketides; Porifera; Spiro Compounds; Structure-Activity Relationship

Topics: Benzofurans; Chromatography, High Pressure Liquid; Chrysosporium; Herbicides; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Molecular Structure; Soil Microbiology; Spiro Compounds

Antibiotic C3368-A (CA) is produced by a fungus strain from a soil sample collected in Antarctica. CA markedly inhibited radiolabeled thymidine and uridine transport in mouse Ehrlich carcinoma cells, its 50% inhibitory concentration (IC50) being 4.6 and 7.7 microM, respectively. In clonogenic assay, CA displayed a synergistic effect with methotrexate (MTX), mitomycin C (MMC), 5-fluorouracil (5FU), and Adriamycin (ADR) against human oral epidermoid carcinoma KB cells. CA also markedly enhanced the inhibitory effect of 5FU and ADR on the proliferation of human hepatoma BEL-7402 cells as determined by the p-nitrophenyl-N-acetyl-beta-D-glucosaminide (NAG) enzyme-reaction assay. 5FU or ADR cytotoxicity was not augmented by CA in human fetal lung 2BS cells. In vivo, CA significantly potentiated the inhibitory effect of MMC against colon carcinoma 26 in mice. No significant augmentation of toxicity by the combination was found in treated mice. The results suggest that CA, the newly found nucleoside-transport inhibitor, may be useful in potentiation of the effect of antitumor drugs.

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Benzofurans; Biological Transport; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Cell Division; Colonic Neoplasms; Doxorubicin; Drug Synergism; Female; Fluorouracil; Humans; KB Cells; Liver Neoplasms; Methotrexate; Mice; Mice, Inbred BALB C; Mitomycin; Spiro Compounds; Thymidine; Tumor Cells, Cultured; Tumor Stem Cell Assay; Uridine

Sulochrin oxidase is a blue copper-containing glycoenzyme that catalyzes a stereospecific formation of bisdechlorogeodin from sulochrin. The enzyme has been isolated from Penicillium frequentans and Oospora sulphurea-ochracea which catalyzes the formation of (+)-form and (-)-form of bisdechlorogeodin respectively. The Penicillium enzyme has a molecular weight of 157,000 and contains 19.5% of carbohydrates. Amino acid and carbohydrate compositions are given. The enzyme has probably a dimeric structure containing 6 Cu-atoms. Apparent Km-values of various substrates are presented. The Oospora enzyme has a molecular weight of 128,000 and except for its stereospecificity its properties are very similar to those of the Penicillium enzyme.

Topics: Alcohol Oxidoreductases; Amino Acids; Benzofurans; Carbohydrates; Mitosporic Fungi; Molecular Weight; Penicillium; Species Specificity; Spiro Compounds; Substrate Specificity