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1.
Bioorg Med Chem ; 23(1): 126-31, 2015 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-25482429

RESUMEN

Chemical investigation of the EtOAc extract of the fungus Chaetomium aureum, an endophyte of the Moroccan medicinal plant Thymelaea lythroides, afforded one new resorcinol derivative named chaetorcinol, together with five known metabolites. The structures of the isolated compounds were determined on the basis of one- and two-dimensional NMR spectroscopy and high-resolution mass spectrometry as well as by comparison with the literature. All compounds were tested for their activity towards the Hsp90 chaperoning machine in vitro using the progesterone receptor (PR) and rabbit reticulocyte lysate (RRL). Among the isolated compounds, only sclerotiorin efficiently inhibited the Hsp90 machine chaperoning activity. However, sclerotiorin showed no cytotoxic effect on breast cancer Hs578T, MDA-MB-231 and prostate cancer LNCaP cell lines. Interestingly, deacetylation of sclerotiorin increased its cytotoxicity toward the tested cell lines over a period of 48 h.


Asunto(s)
Chaetomium/química , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Resorcinoles/química , Resorcinoles/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Femenino , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Conejos
2.
Eur J Med Chem ; 56: 332-47, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22910136

RESUMEN

A series of steroidal 3,16-bis-quaternary ammonium salts were synthesized and screened on mouse hemi-diaphragm to explore new steroidal neuromuscular blocking agents. There were two compounds, 3ß-piperidino derivate 8d (IC(50) = 3.49 µM) and 3ß-N-methylbenzylamino derivate 8g (IC(50) = 4.54 µM), showing activity close to rocuronium (IC(50) = 2.50 µM). The preliminary structure-activity relationship was deduced from the bioactivity results with the aid of the calculated N-N distance and log P. Meanwhile, the interactions between the ligand and binding pocket were revealed by docking 8d to the ligand binding domain of the mouse muscle nicotinic acetylcholine receptor (nAChR). This nAChR was modeled using Molecular Operating Environment (MOE) package indirectly from mollusca acetylcholine binding protein with mouse neuron α7 nAChR as intermediary template.


Asunto(s)
Sondas Moleculares/farmacología , Morfolinas/farmacología , Bloqueantes Neuromusculares/farmacología , Compuestos de Amonio Cuaternario/farmacología , Receptores Nicotínicos/metabolismo , Esteroides/farmacología , Animales , Diafragma/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ligandos , Masculino , Ratones , Sondas Moleculares/síntesis química , Sondas Moleculares/química , Estructura Molecular , Morfolinas/síntesis química , Morfolinas/química , Músculo Esquelético/efectos de los fármacos , Bloqueantes Neuromusculares/síntesis química , Bloqueantes Neuromusculares/química , Neuronas/efectos de los fármacos , Compuestos de Amonio Cuaternario/síntesis química , Compuestos de Amonio Cuaternario/química , Esteroides/síntesis química , Esteroides/química , Relación Estructura-Actividad
3.
Org Lett ; 14(15): 3826-9, 2012 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-22813401

RESUMEN

A series of novel amphiphiles were synthesized based entirely on renewable resources. Besides their efficacy as supramolecular gelators in a wide variety of organic solvents and also water, their surface properties as surfactants and emulsifiers have been determined. A methodical study revealed that the length of the hydrocarbon chains has a dramatic and decisive influence on the thermal stabilities of the obtained hydrogels.


Asunto(s)
Glucosa/análogos & derivados , Glucosa/química , Hidrogeles/síntesis química , Tensoactivos/química , Hidrogeles/química , Interacciones Hidrofóbicas e Hidrofílicas , Lípidos/química , Estructura Molecular , Peso Molecular , Estereoisomerismo , Agua/química
4.
Angew Chem Int Ed Engl ; 50(30): 6701-3, 2011 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-21710672
5.
Carbohydr Res ; 346(11): 1307-10, 2011 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-21601835

RESUMEN

Along with ß-glucans, chitin is the dominant component of the fungal cell wall. Chitosan, the deacetylated form of chitin, has found quite a number of biomedical and biotechnological applications recently. Mushroom chitin could be an important source for chitosan production. A direct determination of chitin and chitosan in mushrooms is of expedient interest. In this paper, a new method for the quantification of chitin and chitosan is described. This method is based on the specific reaction between polyiodide anions and chitosan and on measuring the optical density of the insoluble polyiodide-chitosan complex. After deacetylation, chitin can also be quantified. The specificity of the reaction is used to quantify the polymers in the presence of complex matrices. With this new spot assay, the chitin content of mycelia and fruiting bodies from several basidiomycetes and an ascomycete were analysed. The presented method could also be used for the determination in other samples as well. The chitin content of the analysed species varies between 0.4 and 9.8 g chitin per 100 g of dry mass. Chitosan could not be detected in our mushroom samples, indicating that the glucosamine units are mostly acetylated.


Asunto(s)
Agaricales/química , Quitina/química , Quitosano/química , Micelio/química , Polisacáridos/química
6.
Steroids ; 76(7): 709-23, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21473874

RESUMEN

A series of new 16E-arylidene androstane derivatives were synthesized and characterized. The new compounds were screened for their anticancer activities against the human cancer cell lines SW480, A549, HepG2 and HeLa in vitro using the MTT assay. The results of the in vitro study showed that a number of compounds have shown IC(50) values lower than 20 µM against the four cancer cell lines.


Asunto(s)
Androstanos/síntesis química , Androstanos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Androstanos/química , Antineoplásicos/química , Línea Celular Tumoral , Humanos , Concentración 50 Inhibidora , Relación Estructura-Actividad
7.
Org Lett ; 13(8): 1980-3, 2011 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-21417473

RESUMEN

A library of novel, lipid-modified derivatives of ascorbic acid was shown to exhibit highly attractive properties as surfactants, emulsifiers, oil soluble antioxidants, and highly effective gelators in organic solvents and especially water. In these systems, intermolecular hydrogen bonding and van der Waals forces act synergistically to induce gelation as confirmed by spectroscopic studies. The morphology of the formed gel has been characterized by scanning electron microscopy.


Asunto(s)
Ácido Ascórbico/química , Antioxidantes/química , Calibración , Geles/química , Microscopía Electrónica de Rastreo , Estructura Molecular , Peso Molecular
8.
Food Chem ; 127(2): 791-6, 2011 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-23140737

RESUMEN

Mushroom ß-glucans are known for their activity as biological response modifiers and anticarcinogenic agents. ß-1,3-1,6 Branched glucans with a triple helix tertiary structure are recognised as the most potent ones. In the present work, a colorimetric method for ß-1,3-1,6-glucan quantification based on the dye Congo red is introduced. This method is specific for ß-glucans with a triple helix. The ß-1,3-1,6-glucan content of mycelia and fruiting bodies from various mushrooms was determined and compared with the total ß-1,3-glucan content, measured by a fluorimetric method. The results show equal amounts of ß-1,3-1,6- and total ß-1,3-glucans in the analysed species but obvious differences between mycelia and fruiting bodies. On the average, 3% of mycelia and 8% of fruiting body dry mass consist of ß-1,3-1,6-glucans. The average percentage of ß-1,3-1,6-glucans in the total ß-1,3-glucan content differs between mycelia (46%) and fruiting bodies (87%).

9.
Org Biomol Chem ; 8(17): 3965-74, 2010 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-20589308

RESUMEN

Starting from branched para-benzoquinones a practical and highly flexible route is described for the preparation of unsaturated carbapyranoses. The potential of the synthesized galactose analogues to act as competitive inhibitors in lectin-carbohydrate interactions is investigated by means of Surface Plasmon Resonance (SPR) Spectroscopy.


Asunto(s)
Carba-azúcares/química , Lectinas/química , Carba-azúcares/síntesis química , Estructura Molecular
10.
Org Biomol Chem ; 1(11): 1919-29, 2003 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-12945774

RESUMEN

A practical route is described for the preparation of azido-myo-inositols, amino-myo-inositols and azido-conduritol B derivatives. Starting from p-benzoquinone, optically pure compounds in both forms can be prepared via enzymatic resolution of a derived diacetoxy conduritol B derivative. Selective introduction of nitrogen-containing functional groups in four of the six possible positions in the cyclitol moiety is followed by further functionalization to yield the target compounds.


Asunto(s)
Aminas/química , Azidas/química , Benzoquinonas/química , Fosfatos de Inositol/síntesis química , Inositol/análogos & derivados , Inositol/síntesis química , Ciclohexanoles/química , Ciclohexenos , Fosfatos de Inositol/química , Espectroscopía de Resonancia Magnética , Estructura Molecular , Estereoisomerismo
11.
Bioorg Chem ; 31(1): 44-67, 2003 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-12697168

RESUMEN

Phytases are enzymes that catalyze the hydrolysis of phosphate esters in myo-inositol hexakisphosphate (phytic acid). The precise routes of enzymatic dephosphorylation by phytases of the yeast strains Saccharomyces cerevisiae and Pichia rhodanensis have been investigated up to the myo-inositol trisphosphate level, including the absolute configuration of the intermediates. Stereoselective assignment of the myo-inositol pentakisphosphates (D-myo-inositol 1,2,4,5,6-pentakisphosphate and D-myo-inositol 1,2,3,4,5-pentakisphosphate) generated was accomplished by a new method based on enantiospecific enzymatic conversion and HPLC analysis. Via conduritol B or E derivatives the total syntheses of two epimers of myo-inositol hexakisphosphate, neo-inositol hexakisphosphate and L-chiro-inositol hexakisphosphate were performed to examine the specificity of the yeast phytases with these substrate analogues. A comparison of kinetic data and the degradation pathways determined gave the first hints about the molecular recognition of inositol hexakisphosphates by the enzymes. Exploitation of the high stereo- and regiospecificity observed in the dephosphorylation of neo- and L-chiro-inositol hexakisphosphate made it possible to establish enzyme-assisted steps for the synthesis of D-neo-inositol 1,2,5,6-tetrakisphosphate, L-chiro-inositol 1,2,3,5,6-pentakisphosphate and L-chiro-inositol 1,2,3,6-tetrakisphosphate.


Asunto(s)
6-Fitasa/química , 6-Fitasa/metabolismo , Ácido Fítico/química , Ácido Fítico/metabolismo , Pichia/enzimología , Saccharomyces cerevisiae/enzimología , Activación Enzimática , Hidrólisis , Modelos Químicos , Modelos Moleculares , Ácido Fítico/análogos & derivados , Pichia/química , Pichia/clasificación , Saccharomyces cerevisiae/química , Sensibilidad y Especificidad , Especificidad de la Especie , Estereoisomerismo , Especificidad por Sustrato
12.
FEBS Lett ; 540(1-3): 47-52, 2003 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-12681481

RESUMEN

The C7-cyclitol 2-epi-5-epi-valiolone is the first precursor of the cyclitol moiety of the alpha-glucosidase inhibitor acarbose in Actinoplanes sp. SE50. The 2-epi-5-epi-valiolone becomes phosphorylated at C7 by the ATP dependent kinase AcbM prior to the next modifications. Preliminary data gave evidences that the AcbO protein could catalyse the first modification step of 2-epi-5-epi-valiolone-7-phosphate. Therefore, the AcbO protein, the encoding gene of which is also part of the acbKMLNOC operon, was overproduced and purified. Indeed the purified protein catalysed the 2-epimerisation of 2-epi-5-epi-valiolone-7-phosphate. The chemical structure of the purified reaction product was proven by nuclear magnetic resonance spectroscopy to be 5-epi-valiolone-7-phosphate.


Asunto(s)
Acarbosa/metabolismo , Actinomycetales/enzimología , Racemasas y Epimerasas/metabolismo , Secuencia de Carbohidratos , Electroforesis en Gel de Poliacrilamida , Datos de Secuencia Molecular , Resonancia Magnética Nuclear Biomolecular , Racemasas y Epimerasas/química , Proteínas Recombinantes de Fusión/aislamiento & purificación
13.
FEBS Lett ; 540(1-3): 53-7, 2003 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-12681482

RESUMEN

In the biosynthesis of the C7-cyclitol moiety, valienol, of the alpha-glucosidase inhibitor acarbose in Actinoplanes sp. SE50/110 various cyclitol phosphates, such as 1-epi-valienol-7-phosphate, are postulated precursors. In the cell extracts of Actinoplanes SE50/110 we found a new kinase activity which specifically phosphorylates 1-epi-valienol; other C7-cyclitol analogs were only weakly or not phosphorylated. The purified product of the kinase reaction turned out to be 1-epi-valienol-7-phosphate in analyses by nuclear magnetic resonance spectroscopy. The enzyme seems not to be encoded by an acb gene and, therefore, plays a role in a salvage pathway rather than directly in the de novo biosynthesis of acarbose.


Asunto(s)
Acarbosa/metabolismo , Actinomycetales/metabolismo , Fosfotransferasas/metabolismo , Acarbosa/química , Secuencia de Carbohidratos , Cromatografía en Capa Delgada , Datos de Secuencia Molecular , Resonancia Magnética Nuclear Biomolecular , Espectrometría de Masa por Ionización de Electrospray
14.
J Biol Chem ; 277(25): 22853-62, 2002 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-11937512

RESUMEN

We have previously demonstrated that the biosynthesis of the C(7)-cyclitol, called valienol (or valienamine), of the alpha-glucosidase inhibitor acarbose starts from the cyclization of sedo-heptulose 7-phosphate to 2-epi-5-epi-valiolone (Stratmann, A., Mahmud, T., Lee, S., Distler, J., Floss, H. G., and Piepersberg, W. (1999) J. Biol. Chem. 274, 10889-10896). Synthesis of the intermediate 2-epi-5-epi-valiolone is catalyzed by the cyclase AcbC encoded in the biosynthetic (acb) gene cluster of Actinoplanes sp. SE50/110. The acbC gene lies in a possible transcription unit, acbKLMNOC, cluster encompassing putative biosynthetic genes for cyclitol conversion. All genes were heterologously expressed in strains of Streptomyces lividans 66 strains 1326, TK23, and TK64. The AcbK protein was identified as the acarbose 7-kinase, which had been described earlier (Drepper, A., and Pape, H. (1996) J. Antibiot. (Tokyo) 49, 664-668). The multistep conversion of 2-epi-5-epi-valiolone to the final cyclitol moiety was studied by testing enzymatic mechanisms such as dehydration, reduction, epimerization, and phosphorylation. Thus, a phosphotransferase activity was identified modifying 2-epi-5-epi-valiolone by ATP-dependent phosphorylation. This activity could be attributed to the AcbM protein by verifying this activity in S. lividans strain TK64/pCW4123M, expressing His-tagged AcbM. The His-tagged AcbM protein was purified and subsequently characterized as a 2-epi-5-epi-valiolone 7-kinase, presumably catalyzing the first enzyme reaction in the biosynthetic route, leading to an activated form of the intermediate 1-epi-valienol. The AcbK protein could not catalyze the same reaction nor convert any of the other C(7)-cyclitol monomers tested. The 2-epi-5-epi-valiolone 7-phosphate was further converted by the AcbO protein to another isomeric and phosphorylated intermediate, which was likely to be the 2-epimer 5-epi-valiolone 7-phosphate. The products of both enzyme reactions were characterized by mass spectrometric methods. The product of the AcbM-catalyzed reaction, 2-epi-5-epi-valiolone 7-phosphate, was purified on a preparative scale and identified by NMR spectroscopy. A biosynthetic pathway for the pseudodisaccharidic acarviosyl moiety of acarbose is proposed on the basis of these data.


Asunto(s)
Acarbosa/química , Acarbosa/metabolismo , Actinobacteria/metabolismo , Adenosina Trifosfato/metabolismo , Secuencia de Aminoácidos , Antibacterianos/farmacología , Catálisis , Cromatografía en Capa Delgada , Clonación Molecular , Ciclohexenos , ADN/metabolismo , Electroforesis en Gel de Poliacrilamida , Hexosaminas/química , Hexosaminas/metabolismo , Inositol/análogos & derivados , Inositol/farmacología , Iones , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Modelos Químicos , Datos de Secuencia Molecular , Fosforilación , Plásmidos/metabolismo , Homología de Secuencia de Aminoácido
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