RESUMEN
There is growing interest in the fate and effects of transformation products generated from emerging pollutant classes, and new tools that help predict the products most likely to form will aid in risk assessment. Here, using a family of structurally related steroids (enones, dienones, and trienones), we evaluate the use of density functional theory to help predict products from reaction with chlorine, a common chemical disinfectant. For steroidal dienones (e.g., dienogest) and trienones (e.g., 17ß-trenbolone), computational data support that reactions proceed through spontaneous C4 chlorination to yield 4-chloro derivatives for trienones and, after further reaction, 9,10-epoxide structures for dienones. For testosterone, a simple steroidal enone, in silico predictions suggest that C4 chlorination is still most likely, but slow at environmentally relevant conditions. Predictions were then assessed through laboratory chlorination reactions (0.5-5 mg Cl2/L) with product characterization via HRMS and NMR, which confirmed near exclusive 4-chloro and 9,10-epoxide products for most trienones and all dienones, respectively. Also consistent with computational expectations, testosterone was effectively unreactive at these same chlorine levels, although products consistent with in silico predictions were observed at higher concentrations (in excess of 500 mg Cl2/L). Although slight deviations from in silico predictions were observed for steroids with electron-rich substituents (e.g., C17 allyl-substituted altrenogest), this work highlights the potential for computational approaches to improve our understanding of transformation products generated from emerging pollutant classes.
Asunto(s)
Desinfectantes , Contaminantes Químicos del Agua , Purificación del Agua , Cloro , Halogenación , Contaminantes Químicos del Agua/análisisRESUMEN
The genus Sphaerostilbella comprises fungi that colonize basidiomata of wood-inhabiting fungi, including important forest pathogens. Studies of fermentation cultures of an isolate (TFC201724) collected on the foothills of Himalayas, and closely related to S. broomeana isolates from Europe, led to the identification of a new cyclic octapeptide along with two closely related analogues (1-3) and four dioxopiperazines (4-7). The structure of the lead compound, broomeanamide A (1), was assigned mainly by analysis of 2D NMR and HRESIMS data. The structure consisted of one unit each of N-MeVal, Ala, N-MePhe, Pro, Val, and Ile and two N-MeLeu units. The amino acid sequence was determined on the basis of 2D NMR and HRESIMSMS data. NMR and HRMS data revealed that the other two new peptides have the same amino acid composition except that the Ile unit was replaced with Val in one instance (2) and the N-MeVal unit was replaced with Val in the other (3). The absolute configuration of 1 was assigned by analysis of the acid hydrolysate by application of Marfey's method using both C18 and C3 bonded-phase columns. Broomeanamide A (1) showed antifungal activity against Cryptococcus neoformans and Candida albicans, with MIC values of 8.0 and 64 µg/mL, respectively.
Asunto(s)
Antifúngicos/farmacología , Hypocreales/química , Péptidos Cíclicos/farmacología , Secuencia de Aminoácidos , Antifúngicos/aislamiento & purificación , Candida albicans/efectos de los fármacos , Cryptococcus neoformans/efectos de los fármacos , India , Estructura Molecular , Péptidos Cíclicos/aislamiento & purificaciónRESUMEN
Cryptococcus neoformans is a serious human pathogen with limited options for treatment. We have interrogated extracts from fungal fermentations to find Cryptococcus-inhibiting natural products using assays for growth inhibition and differential thermosensitivity. Extracts from fermentations of four fungal strains from wild and domestic animal dung from Arkansas and West Virginia, USA were identified as Preussia typharum. The extracts exhibited two antifungal regions. Purification of one region yielded new 24-carbon macrolides incorporating both a phosphoethanolamine unit and a bridging tetrahydrofuran ring. The structures of these metabolites were established mainly by analysis of high-resolution mass spectrometry and 2D NMR data. Relative configurations were assigned using NOESY data, and the structure assignments were supported by NMR comparison with similar compounds. These new metabolites are designated preussolides A and B. The second active region was caused by the cytotoxin, leptosin C. Genome sequencing of the four strains revealed biosynthetic gene clusters consistent with those known to encode phosphoethanolamine-bearing polyketide macrolides and the biosynthesis of dimeric epipolythiodioxopiperazines. All three compounds showed moderate to potent and selective antifungal activity toward the pathogenic yeast C. neoformans.
Asunto(s)
Cryptococcus neoformans , Macrólidos , Animales , Antifúngicos/farmacología , Ascomicetos , Etanolaminas , Humanos , Alcaloides Indólicos , Macrólidos/farmacologíaRESUMEN
Photolysis of trenbolone acetate (TBA) metabolites in the presence of various nitrogen-, sulfur-, or oxygen-containing nucleophiles (e.g., azide, ammonia, or thiosulfate, respectively) results in rapid (half-lives â¼20-60 min), photochemically induced nucleophile incorporation across the parent steroid's trienone moiety. The formation of such nucleophile adducts limits formation of photohydrates, suggesting competition between the nucleophile and water for photochemical addition into the activated steroid structure. Analogous to previously reported photohydration outcomes, LC/MS analyses suggest that such photonucleophilic addition reactions are reversible, with more rapid elimination rates than thermal dehydration of photohydrates, and regenerate parent steroid structures. Beyond photonucleophilic addition pathways, we also found that hydroxylamine and presumed nucleophilic moieties in model dissolved organic matter (DOM; Fluka humic acid) can react via thermal substitution with TBA metabolite photohydrates, although this reaction with model DOM was only observed for photohydrates of trendione. Most nucleophile addition products [i.e., formed via (photo)reaction with thiosulfate, hydroxylamine, and ammonia] are notably more polar relative to the parent metabolite and photohydration products. Thus, if present, both nucleophilic adducts and bound residues in organic matter will facilitate transport and help mask detection of TBA metabolites in surface waters and treatment systems.
Asunto(s)
Acetato de Trembolona , Contaminantes Químicos del Agua , Cromatografía Liquida , Sustancias Húmicas , Espectrometría de Masas , Fotólisis , Acetato de Trembolona/análisisRESUMEN
During investigation of the secondary metabolism of four strains of Penicillium arenicola, two new depsides, arenicolins A (1) and B (2), were isolated and characterized. Their structures were established mainly by analysis of NMR and HRMS data and by comparison with known compounds. These depsides incorporate intriguing structural features, including dual alkyl side chains and a C-glycosyl unit, with 1 also containing an acylated 2-hydroxymethyl-4,5,6-trihydroxycyclohexenone moiety. Although the arenicolins were produced by all strains tested, arenicolin A (1) was obtained using only one of five medium compositions employed, while arenicolin B (2) was produced in all media tested. Neither compound showed antibacterial or antifungal activity, but 1 exhibited cytotoxicity toward mammalian cell lines, including colorectal carcinoma (HCT-116), neuroblastoma (IMR-32), and ductal carcinoma (BT-474), with IC50 values of 7.3, 6.0, and 9.7 µM, respectively.
Asunto(s)
Antineoplásicos/farmacología , Depsidos/farmacología , Penicillium/química , Antineoplásicos/aislamiento & purificación , Productos Biológicos/química , Línea Celular Tumoral , Depsidos/aislamiento & purificación , Glicosilación , Humanos , Estructura MolecularRESUMEN
Campafungin A is a polyketide that was recognized in the Candida albicans fitness test due to its antiproliferative and antihyphal activity. Its mode of action was hypothesized to involve inhibition of a cAMP-dependent PKA pathway. The originally proposed structure appeared to require a polyketide assembled in a somewhat unusual fashion. However, structural characterization data were never formally published. This background stimulated a reinvestigation in which campafungin A and three closely related minor constituents were purified from fermentations of a strain of the ascomycete fungus Plenodomus enteroleucus. Labeling studies, along with extensive NMR analysis, enabled assignment of a revised structure consistent with conventional polyketide synthetic machinery. The structure elucidation of campafungin A and new analogues encountered in this study, designated here as campafungins B, C, and D, is presented, along with a proposed biosynthetic route. The antimicrobial spectrum was expanded to methicillin-resistant Staphylococcus aureus, Candida tropicalis, Candida glabrata, Cryptococcus neoformans, Aspergillus fumigatus, and Schizosaccharomyces pombe, with MICs ranging as low as 4-8 µg mL-1 in C. neoformans. Mode-of-action studies employing libraries of C. neoformans mutants indicated that multiple pathways were affected, but mutants in PKA/cAMP pathways were unaffected, indicating that the mode of action was distinct from that observed in C. albicans.
Asunto(s)
Candida albicans/efectos de los fármacos , Cryptococcus neoformans/efectos de los fármacos , Hifa/efectos de los fármacos , Hifa/crecimiento & desarrollo , Antibacterianos/farmacología , Antifúngicos/farmacología , Ascomicetos/química , Ascomicetos/metabolismo , Bacterias/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/efectos de los fármacos , Fermentación , Hongos/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Policétidos/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
While studying the environmental fate of potent endocrine-active steroid hormones, we observed the formation of an intramolecular [2 + 2] photocycloaddition product (2) with a novel hexacyclic ring system following the photolysis of altrenogest (1). The structure and absolute configuration were established by X-ray diffraction analysis. Theoretical computations identified a barrierless two-step cyclization mechanism for the formation of 2 upon photoexcitation. 2 exhibited progesterone, estrogen, androgen, and pregnane X receptor activity, albeit generally with reduced potency relative to 1.
Asunto(s)
Procesos Fotoquímicos , Acetato de Trembolona/análogos & derivados , Reacción de Cicloadición , Teoría Funcional de la Densidad , Humanos , Receptores Citoplasmáticos y Nucleares/metabolismo , Acetato de Trembolona/síntesis química , Acetato de Trembolona/química , Acetato de Trembolona/metabolismoRESUMEN
In the course of our studies of coprophilous fungi as sources of antifungal agents, a strain of an undescribed species in the genus Niesslia (TTI-0426) was isolated from horse dung collected in Texas. An extract from fermentation cultures of this strain afforded two new antifungal wortmannin derivatives, wortmannins C and D (1 and 2), as well as four additional new related compounds, wortmannines B1-B4 (3-6), containing an unusual ring system. The structures of these metabolites were established mainly by analysis of HRESIMS and 2D NMR data. Relative configurations were assigned using NOESY data, and the structure assignments were supported by NMR comparison with similar compounds. Wortmannins C and D showed activity against Cryptococcus neoformans and Candida albicans in disk assays, but low MIC potency observed for 1 was suggested to be due in part to efflux processes on the basis of assay results for a Schizosaccharomyces pombe efflux mutant in comparison to wild-type.
Asunto(s)
Hypocreales/química , Wortmanina/aislamiento & purificación , Candida albicans/efectos de los fármacos , Cryptococcus neoformans/efectos de los fármacos , Fermentación , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Schizosaccharomyces/efectos de los fármacos , Análisis Espectral/métodos , Wortmanina/química , Wortmanina/farmacologíaRESUMEN
We used a temperature differential assay with the opportunistic fungal pathogen Cryptococcus neoformans as a simple screening platform to detect small molecules with antifungal activity in natural product extracts. By screening of a collection extracts from two different strains of the coprophilous fungus, Amphichorda felina, we detected strong, temperature-dependent antifungal activity using a two-plate agar zone of inhibition assay at 25 and 37 °C. Bioassay-guided fractionation of the crude extract followed by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance spectroscopy (NMR) identified cyclosporin C (CsC) as the main component of the crude extract responsible for growth inhibition of C. neoformans at 37 °C. The presence of CsC was confirmed by comparison with a commercial standard. We sequenced the genome of A. felina to identify and annotate the CsC biosynthetic gene cluster. The only previously characterized gene cluster for the biosynthesis of similar compounds is that of the related immunosuppressant drug cyclosporine A (CsA). The CsA and CsC gene clusters share a high degree of synteny and sequence similarity. Amino acid changes in the adenylation domain of the CsC nonribosomal peptide synthase's sixth module may be responsible for the substitution of L-threonine compared to L-α-aminobutyric acid in the CsA peptide core. This screening strategy promises to yield additional antifungal natural products with a focused spectrum of antimicrobial activity.
Asunto(s)
Antifúngicos/farmacología , Cryptococcus neoformans/efectos de los fármacos , Ciclosporinas/farmacología , Hypocreales/química , Antifúngicos/química , Antifúngicos/metabolismo , Cryptococcus neoformans/crecimiento & desarrollo , Ciclosporinas/química , Ciclosporinas/metabolismo , Hypocreales/genética , Hypocreales/metabolismo , TemperaturaRESUMEN
Studies of the genome-sequenced, flutimide-producing coprophilous fungus Delitschia confertaspora (ATCC 74209), originally obtained from a sample of rock hyrax (Procavia capensis) dung collected in Namibia, led to the discovery of three new highly aromatic natural products named delicoferones A-B (1-2) and fimetarone B (3). The new benzophenone derivatives 1 and 2 have a somewhat unusual skeleton that incorporates three aromatic rings linked via two ketone carbonyl groups, while 3 contains a spiro[chroman-3,7'-isochromene]-4,6'(8'H) skeleton reported only once previously. The structures of these compounds were assigned mainly by analysis of 2D NMR and HRESITOFMS data.
Asunto(s)
Benzofenonas/aislamiento & purificación , Hongos/química , Compuestos de Espiro/aislamiento & purificación , Animales , Benzofenonas/química , Damanes , Estructura Molecular , Namibia , Resonancia Magnética Nuclear Biomolecular , Compuestos de Espiro/químicaRESUMEN
Auxarthrones A-E (1-5), five new phenalenones, and two new naturally occurring cyclic tetrapeptides, auxarthrides A (7) and B (8), were obtained from three different solvent extracts of cultures of the coprophilous fungus Auxarthron pseudauxarthron. Auxarthrones C (3) and E (5) possess an unusual 7a,8-dihydrocyclopenta[a]phenalene-7,9-dione ring system that has not been previously observed in natural products. Formation of 1-5 was found to be dependent on the solvent used for culture extraction. The structures of these new compounds were elucidated primarily by analysis of NMR and MS data. Auxarthrone A (1) was obtained as a mixture of chromatographically inseparable racemic diastereomers (1a and 1b) that cocrystallized, enabling confirmation of their structures by X-ray crystallography. The absolute configurations of 7 and 8 were assigned by analysis of their acid hydrolysates using Marfey's method. Compound 1 displayed moderate antifungal activity against Cryptococcus neoformans and Candida albicans, but did not affect human cancer cell lines.
Asunto(s)
Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Ascomicetos/química , Cryptococcus neoformans/efectos de los fármacos , Péptidos Cíclicos/aislamiento & purificación , Péptidos Cíclicos/farmacología , Fenalenos/aislamiento & purificación , Fenalenos/farmacología , Antifúngicos/química , Neoplasias de la Mama/tratamiento farmacológico , Candida albicans/efectos de los fármacos , Cristalografía por Rayos X , Femenino , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Péptidos Cíclicos/química , Fenalenos/químicaRESUMEN
BACKGROUND: Increased atmospheric carbon dioxide (CO2) levels predicted to occur before the end of the century will impact plant metabolism. In addition, nitrate availability will affect metabolism and levels of nitrogen-containing defense compounds, such as glucosinolates (GSLs). We compared Arabidopsis foliar metabolic profile in plants grown under two CO2 regimes (440 vs 880 ppm), nitrate fertilization (1 mM vs 10 mM) and in response to mechanical damage of rosette leaves. RESULTS: Constitutive foliar metabolites in nitrate-limited plants show distinct global patterns depending on atmospheric CO2 levels; in contrast, plants grown under higher nitrate fertilization under elevated atmospheric CO2 conditions have a unique metabolite signature. Nitrate fertilization dampens the jasmonate burst in response to wounding in plants grown at elevated CO2 levels. Leaf GSL profile mirrors the jasmonate burst; in particular, indole GSLs increase in response to damage in plants grown at ambient CO2 but only in nitrate-limited plants grown under elevated CO2 conditions. CONCLUSIONS: This may reflect a reduced capacity of C3 plants grown under enriched CO2 and nitrate levels to signal changes in oxidative stress and has implications for future agricultural management practices.
Asunto(s)
Arabidopsis/metabolismo , Dióxido de Carbono/metabolismo , Fertilizantes , Glucosinolatos/biosíntesis , Nitratos/metabolismo , Atmósfera , Enfermedades de las Plantas , Hojas de la Planta/metabolismoRESUMEN
Seven new polyketide metabolites (disseminins A-E, 1-5, and spiciferones D and E, 7 and 8) were obtained from cultures of a fungicolous isolate of Pestalotiopsis disseminata (NRRL 62562), together with a related compound (6) previously known only as a semisynthetic product. Structures were determined mainly by analysis of HRMS and NMR data. Biogenetically related compounds 1 and 2 possess uncommon bis-tetrahydrofuran and dioxabicyclo[3.2.1]octane ring systems, respectively. X-ray crystallographic analysis of the p-bromobenzoate derivative of 1 confirmed the structure and enabled assignment of its absolute configuration.
Asunto(s)
Policétidos/química , Xylariales/química , Cristalografía por Rayos X , Georgia , Conformación Molecular , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
Eleven emestrin-type epipolythiodioxopiperazines, including four new compounds, emestrins H-K (1-4), were isolated from the crude extracts of two strains of the coprophilous fungus Podospora australis. The structures of 1-4 were established primarily by analysis of NMR data, and the absolute configuration of C-6 in 1 was independently assigned using the modified Mosher method. Four of the known emestrins obtained (emestrins C-E and MPC1001C) were found to selectively inhibit the growth of Cryptococcus neoformans. These results also represent the first report of chemistry from any strain of P. australis.
Asunto(s)
Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Cryptococcus neoformans/efectos de los fármacos , Piperazinas/aislamiento & purificación , Piperazinas/farmacología , Podospora/química , Animales , Antifúngicos/química , Defecación , Caballos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Piperazinas/químicaRESUMEN
Studies of the coprophilous fungus Hypocopra rostrata (TTI-0009, NRRL 66178) isolated from a sample of horse dung collected in Texas led to the isolation of three new sesquiterpenoids that we named hypocoprins A-C (1-3), together with the known fungal metabolite helvolic acid. The new metabolites have a distinctive ring system consisting of fused cyclopropane and cyclodecene units not previously reported from a fungal source. Compounds 1 and 3 moderately inhibited growth of Staphylococcus aureus. The structures of these metabolites were assigned mainly by analysis of 2D NMR and HRESITOFMS data. Relative and absolute configurations were assigned by interpretation of NMR J-values and NOESY data and by application of Mosher's method. These results represent the first report of chemistry from any strain of the genus Hypocopra.
Asunto(s)
Sesquiterpenos/aislamiento & purificación , Xylariales/química , Animales , Antifúngicos/farmacología , Ácido Fusídico/análogos & derivados , Ácido Fusídico/aislamiento & purificación , Caballos , Estiércol/microbiología , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Sesquiterpenos/química , Staphylococcus aureus/efectos de los fármacos , TexasRESUMEN
Continuing investigation of fractions from a supercritical fluid extract of Chinese licorice (Glycyrrhiza uralensis) roots has led to the isolation of 12 phenolic compounds, of which seven were described previously from this extract. In addition to these seven metabolites, four known components, 1-methoxyerythrabyssin II (4), 6,8-diprenylgenistein, gancaonin G (5), and isoglycyrol (6), and one new isoflavan, licorisoflavan C (7), were characterized from this material for the first time. Treatment of licoricidin (1) with palladium chloride afforded larger amounts of 7 and also yielded two new isoflavans, licorisoflavan D (8), which was subsequently detected in the licorice extract, and licorisoflavan E (9). Compounds 1-9 were evaluated for their antibacterial activities against the cariogenic Streptococcus mutans and the periodontopathogenic Porphyromonas gingivalis. Licoricidin (1), licorisoflavan A (2), and 7-9 showed antibacterial activity against P. gingivalis (MICs of 1.56-12.5 µg/mL). The most potent activity against S. mutans was obtained with 7 (MIC of 6.25 µg/mL), followed by 1 and 9 (MIC of 12.5 µg/mL). This study provides further evidence for the therapeutic potential of licorice extracts for the treatment and prevention of oral infections.
Asunto(s)
Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Glycyrrhiza uralensis/química , Isoflavonas/aislamiento & purificación , Isoflavonas/farmacología , Porphyromonas gingivalis/efectos de los fármacos , Piranos/aislamiento & purificación , Piranos/farmacología , Streptococcus mutans/efectos de los fármacos , Antibacterianos/química , Benzopiranos/química , Genisteína/análogos & derivados , Genisteína/química , Alemania , Glycyrrhiza/metabolismo , Isoflavonas/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Paladio/farmacología , Fenoles/química , Fenoles/aislamiento & purificación , Fenoles/farmacología , Raíces de Plantas/química , Pterocarpanos/química , Pterocarpanos/aislamiento & purificación , Piranos/químicaRESUMEN
The first total synthesis of marine-derived penicimonoterpene (±)-1 has been achieved in four steps from 6-methylhept-5-en-2-one using a Reformatsky reaction as the key step to construct the basic carbon skeleton. A total of 24 new derivatives of 1 have also been designed and synthesized. Their structures were characterized by analysis of their 1H NMR, 13C NMR and HRESIMS data. Some of them showed significant antibacterial activity against Aeromonas hydrophila, Escherichia coli, Micrococcus luteus, Staphylococcus aureus, Vibrio anguillarum, V. harveyi and/or V. parahaemolyticus, and some showed activity against plant-pathogenic fungi (Alternaria brassicae, Colletotrichum gloeosporioides and/or Fusarium graminearum). Some of the derivatives exhibited antimicrobial MIC values ranging from 0.25 to 4 µg/mL, which were stronger than those of the positive control. Notably, Compounds 3b and 10 showed extremely high selectively against plant-pathogenic fungus F. graminearum (MIC 0.25 µg/mL) and pathogenic bacteria E. coli (MIC 1 µg/mL), implying their potential as antimicrobial agents. SAR analysis of 1 and its derivatives indicated that modification of the carbon-carbon double bond at C-6/7, of groups on the allylic methylene unit and of the carbonyl group at C-1, effectively enhanced the antimicrobial activity.
Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Caprilatos/farmacología , Monoterpenos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antifúngicos/síntesis química , Antifúngicos/química , Bacterias/efectos de los fármacos , Caprilatos/síntesis química , Caprilatos/química , Hongos/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Monoterpenos/síntesis química , Monoterpenos/química , Relación Estructura-ActividadRESUMEN
Despite the widespread use of the anabolic androgen trenbolone acetate (TBA) in animal agriculture, evidence demonstrating the occurrence of TBA metabolites such as 17ß-trenbolone (17ß-TBOH), 17α-trenbolone (17α-TBOH), and trendione (TBO) is relatively scarce, potentially due to rapid transformation processes such as direct photolysis. Therefore, we investigated the phototransformation of TBA metabolites and associated ecological implications by characterizing the photoproducts arising from the direct photolysis of 17ß-TBOH, 17α-TBOH, and TBO and their associated ecotoxicity. LC-HRMS/MS analysis identified a range of hydroxylated products that were no longer photoactive, with primary photoproducts consisting of monohydroxy species and presumptive diastereomers. Also observed were higher-order hydroxylated products probably formed via subsequent reaction of primary photoproducts. NMR analysis confirmed the formation of 12,17-dihydroxy-estra-5(10),9(11),dien-3-one (12-hydroxy-TBOH; 2.2 mg), 10,12,17-trihydroxy-estra-4,9(11),dien-3-one (10,12-dihydroxy-TBOH; 0.7 mg), and a ring-opened 11,12-dialdehyde oxidation product (TBOH-11,12-dialdehyde; 1.0 mg) after irradiation of â¼14 mg of 17ß-trenbolone. Though unconfirmed by NMR, our data suggest that the formation of additional isomeric products may occur, likely due to the reactivity of the unique 4,9,11 conjugated triene structure of trenbolone. In vivo exposure studies employing Japanese medaka (Oryzias latipes) indicate that low concentrations of 17α-TBOH photoproduct mixtures can alter ovarian follicular development, and photoproducts alter whole-body 17ß-estradiol levels. Therefore, direct photolysis yields photoproducts with strong structural similarity to parent steroids, and these photoproducts still retain enough biological activity to elicit observable changes to endocrine function at trace concentrations. These data indicate that environmental transformation processes do not necessarily reduce steroid hormone ecotoxicity.
Asunto(s)
Anabolizantes/metabolismo , Procesos Fotoquímicos , Acetato de Trembolona/metabolismo , Cromatografía Liquida , Espectroscopía de Resonancia Magnética , Espectrofotometría Ultravioleta , Espectrometría de Masas en TándemRESUMEN
Seven new compounds (aflaquinolones A-G; 1-7) containing dihydroquinolin-2-one and terpenoid units have been isolated from two different fungal sources. Two of these metabolites (1 and 2) were obtained from a Hawaiian fungicolous isolate of Aspergillus sp. (section Flavipedes; MYC-2048 = NRRL 58570), while the others were obtained from a marine Aspergillus isolate (SF-5044) collected in Korea. The structures of these compounds were determined mainly by analysis of NMR and MS data. Relative and absolute configurations were assigned on the basis of NOESY data and (1)H NMR J-values, comparison of calculated and experimental ECD spectra, and analysis of a Mosher's ester derivative of 2. Several known compounds, including alantrypinone, aspochalasins I and J, methyl 3,4,5-trimethoxy-2((2-((3-pyridinylcarbonyl)amino)benzoyl)amino)benzoate, and trans-dehydrocurvularin were also encountered in the extract of the Hawaiian isolate.
Asunto(s)
Aspergillus/química , Quinolonas/aislamiento & purificación , República Popular Democrática de Corea , Células HL-60 , Hawaii , Humanos , Biología Marina , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Quinolonas/química , Staphylococcus aureus , EstereoisomerismoRESUMEN
Phomalevones A-C (1-3), three new com-pounds with bis-dihydroxanthone and bis-benzophenone systems, were isolated from cultures of a Hawaiian isolate of Phoma sp. (MYC-1734 = NRRL 39060; Cucurbitariaceae). The structures of 1-3 were determined by analysis of NMR and MS data. The absolute configurations of the sp(3) stereocenters in the monomeric unit of 1 were assigned by application of Mosher's method, and overall absolute configurations were proposed on the basis of ECD data using both computational methods and comparisons with literature data for model compounds. All three compounds showed antibacterial activity, and compounds 2 and 3 also exhibited antifungal effects.