ABSTRACT
Three isomeric hemigossypol derivatives (3,4,5) have been synthesized. Two of these derivatives (3,4) and one synthetic intermediate (7) have been shown to have activity comparable to gossypol (1) in a sperm motility assay.
Subject(s)
Gossypol/analogs & derivatives , Sperm Motility/drug effects , Animals , Cricetinae , Gossypol/chemical synthesis , Gossypol/pharmacology , Isomerism , MaleABSTRACT
A facile procedure is described for the conversion of morphine, via the diphosphate ester derivative 1 followed by catalytic reduction and treatment with Li/NH3, to 3-deoxy-7,8-dihydromorphine (3). Oxidation with benzophenone tert-butoxide converted 3 to the ketone 4, which on treatment with Zn/NH4Cl formed (-)-4-hydroxymorphinan-6-one 5. Reaction of 5 with diazomethane formed the methyl ether 6. The N-cyclopropylmethyl analogues of 4 and 5 were also prepared, i.e., 8c and 9 from 4. The antinociceptive activity of these compounds was tested. Compounds 5, 6, 8c, and 9 showed potent antiwrithing activity and, based on these data, a structure-activity relationship in morphinans is discussed.
Subject(s)
Analgesics/chemical synthesis , Morphinans/chemical synthesis , Animals , Male , Mice , Morphinans/pharmacology , Rats , Reaction Time/drug effectsABSTRACT
A potent toxin isolated from Penicillium islandicum Sopp was found to have the composition C24H31N5O7Cl2. Mass spectrometric investigation of a partial acid hydrolyzate showed that it has the structure of cyclochlorotine. The mass spectral characteristics of polyamino alcohol-related derivatives of peptides containing beta-phenylalanine, alpha-amino butyric acid and dichloroproline were determined in the course of this work.
Subject(s)
Mycotoxins/analysis , Peptides, Cyclic/analysis , Amino Acid Sequence , Aminobutyrates/analysis , Bacterial Toxins/analysis , Chlorine/analysis , Mass Spectrometry , Penicillium , Phenylalanine/analysis , Proline/analogs & derivatives , Proline/analysisABSTRACT
Twelve mycotoxins produced by Penicillium islandicum Sopp and Penicillium rugulosum in solid-state fermentation on grains were purified and tested for mutagenicity and antibacterial activity in Salmonella/mammalian microsome assays. The mutations studied were reversions of histidine auxotrophs to prototrophy in strains TA98 and TA100 and forward mutations to 8-azaguanine resistance (8AGR) in strain TM677. Rubroskyrin, (+)rugulosin, lumiluteoskyrin [a photoproduct of (-)luteoskyrin], and simatoxin [a new water-soluble metabolite of unknown structure] induced 8AGR mutations in strain TM677 but not histidine reversions in strains TA98 and TA100. Mutagenic potency was reduced by rat-liver microsomes. The carcinogens (-)luteoskyrin and cyclochlorotine were antibacterial but not mutagenic. (+)Rugulosin, rubroskyrin, lumiluteoskyrin, and high concentrations of simotoxin were also antibacterial. Antibacterial activity but not mutagenicity was observed with pibasterol and skyrin. Chrysophanol, islandicin, iridoskyrin, and emodin were inactive as mutagens or as antibacterial agents.
Subject(s)
Anti-Bacterial Agents , Mutagens , Mycotoxins/pharmacology , Penicillium/metabolism , Animals , Histidine/metabolism , In Vitro Techniques , Microbial Sensitivity Tests , Microsomes, Liver/metabolism , Mycotoxins/biosynthesis , Rats , Salmonella typhimurium/drug effects , Salmonella typhimurium/geneticsABSTRACT
A rapid, convenient TLC method is described for detection of cyclochlorotine, a carcinogen produced by the commonly found storage mold Penicillium islandicum Sopp. This method has also led to the isolation of a new toxic metabolite, simatoxin.
Subject(s)
Mycotoxins/analysis , Penicillium/analysis , Chromatography, Thin Layer/methodsABSTRACT
Production of the hepatotoxin cyclochlorotine by Penicillium islandicum was studied under a variety of fermentation conditions. The best system for production was agitated red wheat. A thin-layer chromatographic method was developed for the detection of this cyclic polypeptide. These experiments have resulted in the isolation of a new toxic metabolite, which we call simatoxin.
Subject(s)
Mycotoxins/biosynthesis , Penicillium/metabolism , Peptides, Cyclic/biosynthesis , Animals , Chemical Phenomena , Chemistry , Culture Media , Fermentation , Liver/drug effects , Mycotoxins/isolation & purification , Mycotoxins/toxicity , Peptides, Cyclic/isolation & purification , Peptides, Cyclic/toxicity , Rats , TriticumABSTRACT
Production of luteoskyrin, a hepatotoxin synthesized by Penicillium islandicum Sopp., was studied with various fermentation methods. Best results were obtained in static fermentations on glutinous rice at 30 degrees C. The isolated yield of pure luteoskyrin was approximately 400 mg per kg of rice. Also produced were skyrin, islandicin, iridoskyrin, rubroskyrin, chrysophanol, mannitol, and erythritol. A new metabolite, which we call pibasterol, was also isolated.
