RESUMO
Chemoenzymatic glucuronidation of the optically pure silybin A (1) using ovine liver glucuronyl transferase afforded three beta-glucuronides of silybin, substituted at phenolic OH groups at the positions C-20 (2), C-7 (3), and C-5 (4) formed in the yields 27, 62.5, and 2.5%, respectively. Using these standards, it was shown that the main silybin conjugate in humans is its 20-beta-D-glucuronate (2), while the C-7 regioisomer (3) was formed in lower proportion. The rate of conjugation of (natural) silybin diastereomers 10S, 11S and 10R, 11R, and therefore also their metabolism in humans is rather different. The radical scavenging activity of 2 is considerably lower than that of its aglycone (1); however, the activity of 3 is higher than in the silybin. These findings corroborate the hypothesis that, at physiological pH, the exclusive target for one-electron oxidation of the silybin molecule is the o-methoxy-phenolic structure at C-19, C-20. This is first pharmacological study using optically pure silybin.
Assuntos
Sequestradores de Radicais Livres/farmacologia , Silimarina/farmacologia , Cromatografia Líquida de Alta Pressão , Sequestradores de Radicais Livres/sangue , Sequestradores de Radicais Livres/química , Glucuronídeos/sangue , Glucuronídeos/química , Glucuronídeos/farmacologia , Glucuronosiltransferase/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Silimarina/sangue , Silimarina/química , EstereoisomerismoRESUMO
Pyranose dehydrogenase purified to homogeneity from the mycelia of the basidiomycete fungus Agaricus bisporus catalyzed the oxidation of D-xylose at C-2 to D-threo-pentos-2-ulose (2-keto-D-xylose) and successively at C-3 to D-glycero-pentos-2,3-diulose (2,3-diketo-D-xylose) using 1,4-benzoquinone as an electron acceptor. The sites of oxidation were deduced from the spectroscopic analysis (MS, NMR) of the N,N-diphenylhydrazone derivatives of the reaction products.
Assuntos
Agaricus/enzimologia , Desidrogenases de Carboidrato/metabolismo , Xilose/metabolismo , Desidrogenases de Carboidrato/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Hidrazonas/química , Cetonas/química , Cetonas/metabolismo , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Oxirredução , Xilose/análogos & derivados , Xilose/químicaRESUMO
Rubropunctatin (1), monascorubrin (2), monascin (3) and ankaflavin (4) were purified from the mycelium of Monascus purpureus by flash chromatography on silica gel or reversed phase. Their embryotoxicity towards chicken embryos decreased in the order 2 > 1 > 3 > 4. The lower homologues 1 and 3 exhibited teratogenic effects on these organisms. Significant antibiotic activities against Bacillus subtilis and Candida pseudotropicalis were found with compounds 1 and 2. Immunosuppressive activity on mouse T-splenocytes was most pronounced with compounds 3 and 4. None of the compounds showed significant cytotoxic activity towards rat hepatocytes in vitro. Incubation of resting cells of M. purpureus with glycine afforded the dark-red compounds 5 and 6 where the pyran moiety of 1 and 2 changed into the N-substituted dihydropyridine moiety by replacement of the O-atom by the amino group of glycine. Compounds 5 and 6 were less biologically active than the major pigments 1-4.
Assuntos
Ascomicetos/química , Corantes de Alimentos/farmacologia , Pigmentos Biológicos/farmacologia , Anormalidades Induzidas por Medicamentos/etiologia , Animais , Bacillus subtilis/efeitos dos fármacos , Candida/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Embrião de Galinha , Hepatócitos/efeitos dos fármacos , Tolerância Imunológica/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Pigmentos Biológicos/química , Ratos , Linfócitos T/efeitos dos fármacosRESUMO
Two d-glucose-oxidizing enzymes, glucose 1-oxidase (G1O) and pyranose 2-oxidase (P2O, glucose 2-oxidase), have been proposed to play an important role in the ligninolytic system of the white rot fungus Phanerochaete chrysosporium by producing hydrogen peroxide. The possible simultaneous expression and metabolic cooperation of the two oxidases was studied in strains ME-446 (reported as G1O positive) and K-3 (P2O positive) grown in liquid media and under near natural conditions on birch wood blocks. The presence of G1O and P2O in extracts from mycelia and decayed wood was determined by chromatographic, electrophoretic, and immunological methods. Attempts to separate these enzymes and to detect G1O and its reaction product, d-glucono-1,5-lactone, failed. Evidence was obtained only for P2O expression in both strains. Accordingly, P2O, rather than G1O, represents a major source of sugar-derived H2O2 under the culture conditions used.
Assuntos
Basidiomycota/metabolismo , Glucose Oxidase/metabolismo , Lignina/metabolismo , Cromatografia Líquida de Alta Pressão , Peróxido de Hidrogênio/metabolismoRESUMO
Seven streptomycete strains were tested for biotransformation of salicylate. The products were identified by nuclear magnetic resonance spectroscopy and three types of conversion were found. Streptomyces cinnamonensis and Streptomyces spectabilis formed gentisate and salicylamide concurrently. Streptomyces rimosus transformed salicylate to salicylamide. Streptomyces lividans, Streptomyces coelicolor, Streptomyces griseus and Streptomyces avermitilis produced only gentisate. Time course studies of salicylate conversion by thin-layer chromatography and high pressure liquid chromatography showed that salicylamide was accumulated in the culture broth, whereas gentisate was further metabolized.Key words: salicylate, gentisate, salicylamide, biotransformation, Streptomyces spp.
RESUMO
Virginiamycins S1 and M1, two major components of the antibacterial antibiotic complex produced by Streptomyces virginiae and used as an animal growth promoter in animal husbandry, exhibited a selective insecticidal activity against Leptinotarsa decemlineata comparable with the effect of the organophosphorus pesticide Metathion. An acaricidal effect of the two compounds on eggs of Tetranychus urticae was also observed.
Assuntos
Inseticidas , Virginiamicina/farmacologia , Ácaros e Carrapatos , Animais , Avaliação Pré-Clínica de Medicamentos , Feminino , Insetos , Larva , Óvulo , Virginiamicina/administração & dosagemRESUMO
By using both the traditional International Streptomycetes Project methods and chemical approaches followed by a hierarchical cluster analysis, Streptomyces virginiae mutants A-1 and B-43 (yielding higher amounts of the M1 component of virginiamycin complex), their wild ancestor ATCC 13161, and another virginiamycin producer, S. pristinaespiralis NRRL 2958, were subjected to taxonomic studies to find kinship or differences among the strains. Of the methods used, only the test of carbon utilization, investigation of spore surface and analysis of sugar constituents of cell walls proved to be reliable enough to demonstrate the species identity of S. virginiae strains and to distinguish them from S. pristinaespiralis. L,L-2,6-Diaminopimelic acid was present in all strains. Analysis of fatty acids and total proteins as well as investigations of morphology and pigmentation of agar cultures led to confusing results.
Assuntos
Mutação , Streptomyces/classificação , Virginiamicina/biossíntese , Eletroforese em Gel de Poliacrilamida , Streptomyces/genética , Streptomyces/crescimento & desenvolvimento , Streptomyces/metabolismoRESUMO
Semisynthetic derivatives of daunomycinone with 7,9-isopropylacetal, 7-O-methyl, 7-O-(4-penten-2-yl), and 7-O-(2-hydroxyethyl) substituents were converted by Streptomyces peucetius var. caesius (an adriamycin-blocked mutant) into 7-deoxy-13-dihydrodaunomycinone, while daunomycinone was transformed into 13-dihydrodaunomycinone (predominantly) and 7-deoxy-13-dihydrodaunomycinone. S. coeruleorubidus mutants 24-74 (accumulating aclavinone derivatives instead of daunomycin and related compounds) and 96-85 (producing no anthracycline substances), and S. aureofaciens B-96 (a tetracycline-blocked mutant) transformed the above substrates into the corresponding 13-dihydro derivatives, with the exception of 7,9-isopropylacetal daunomycinone which remained intact. 7-O-Propyn-1-yl daunomycinone was not transformed by any of the strains used under the conditions.
Assuntos
Naftacenos/metabolismo , Streptomycetaceae/metabolismoRESUMO
The cytotoxic effect of (7S)- and (7R)-O-epoxyalkyl derivatives of daunomycinone on leukemia P388 cells was followed in in vitro tests and their mutagenicity was determined by means of the bacterial SOS chromotest. The biological effects of the substances were compared with those of daunomycin, carminomycin and nogalamycin. The most efficient derivative proved to be the (7S)-9-acetyl-4-methoxy 7-O-(2,3-epoxypropyl)-7,8,9,10-tetrahydro-6,9,11-trihydroxy-5, 12-naphthacenequinone 10 which inhibited the DNA and RNA synthesis and proliferation of P388 cells on the level of daunomycin or carminomycin. The cytotoxic and mutagenic action of 7-O-epoxyalkyl derivatives of daunomycinone was affected by the length of alkyl and its configuration.
Assuntos
Naftacenos/uso terapêutico , Animais , Carrubicina/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Daunorrubicina/uso terapêutico , Leucemia P388/tratamento farmacológico , Camundongos , Testes de Mutagenicidade , Nogalamicina/uso terapêutico , RNA/biossíntese , Relação Estrutura-AtividadeRESUMO
Synthesis and antibacterial activity of a number of 7-O-epoxyalkyl derivatives of daunomycinone prepared from 7-O-alkenyl derivatives of daunomycinone are described along with their inhibitory effect on leukemia P 388 cells.
Assuntos
Antibióticos Antineoplásicos/síntese química , Naftacenos/síntese química , Animais , Antibióticos Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Leucemia P388/metabolismo , Naftacenos/farmacologiaRESUMO
The strain Streptomyces griseoruber 4620 produces, besides the anthracycline antibiotics beromycins, some other anthracyclines of the rhodomycin type. Twelve isolates exhibiting a higher antibiotic activity (up to 2.5X), as compared to the parent strain, were obtained after a spontaneous selection. The following species were isolated from the hydrolysate of mycelial extract: beta-rhodomycinone, beta-isorhodomycinone, alpha 2-rhodomycinone, epsilon-rhodomycinone and 10-deoxy-beta-rhodomycinone, which has not yet been described.
Assuntos
Antibacterianos/biossíntese , Naftacenos/biossíntese , Streptomyces/metabolismo , Antraciclinas , Antibacterianos/isolamento & purificação , Naftacenos/isolamento & purificaçãoRESUMO
A new metabolite denoted as verotetrone was isolated from the mycelium of the mutant strain Streptomyces aureofaciens NMG-2. Interpretations of physical data concerning verotetrone and its triacetate and, the determination of its degradation product indicate that verotetrone belongs to pretetramide-type metabolites. Verotetrone exhibits neither antibacterial nor antifungal activity. In vitro it inhibits the synthesis of nucleic acids as well as proteins in Ehrlich ascites carcinoma cells. Both verotetrone and its triacetate interfere in vivo with the metabolism of tumour and lymphoid cells, exhibiting antitumour or immunosuppressive activity. This activity, which is more intense with verotetrone than with its triacetate, is detectable in a dose which is already toxic in some animals.
Assuntos
Antraciclinas , Antibióticos Antineoplásicos , Streptomyces aureofaciens/metabolismo , Animais , Bactérias/efeitos dos fármacos , Candida/efeitos dos fármacos , Carcinoma de Ehrlich/metabolismo , Feminino , Leucemia Experimental/tratamento farmacológico , Leucemia Experimental/imunologia , Camundongos , Camundongos Endogâmicos , Mutação , Naftacenos/análise , Naftacenos/isolamento & purificação , Naftacenos/farmacologia , Neoplasias Experimentais , Ácidos Nucleicos/biossíntese , Imunologia de TransplantesRESUMO
From a mixture of substances formed by producing strains of Streptomyces aureofaciens under conditions of submerged fermentation a new metabolite, ekatetrone, was isolated. Its isolation and basic physical and chemical data are described. Ekatetrone is a quinone derivative with a carboxamide group. In tests in vitro with cells of Ehrlich's ascites tumour evidence was provided that ekatetrone inhibits proteo- and nucleosynthesis.
Assuntos
Antibióticos Antineoplásicos/isolamento & purificação , Streptomyces aureofaciens/metabolismo , Animais , Antraquinonas/biossíntese , Antraquinonas/isolamento & purificação , Antibióticos Antineoplásicos/biossíntese , Carcinoma de Ehrlich/metabolismo , Fenômenos Químicos , Química , Fermentação , Técnicas In Vitro , Testes de Sensibilidade Microbiana , Valina/metabolismoRESUMO
The structure of ekatetrone has been determined from physico-chemical data obtained using the natural compound, its derivatives and products of degradation reactions. Ekatetrone was found to be the lactone of 1,8-dihydroxy-2-(1'-hydroxy-2'-carbamoyl)ethyl-9,10-anthraquinone-3-acetic acid (I). It is proposed that ekatetrone is related, biogenetically, to protetrone.