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1.
Eur J Prosthodont Restor Dent ; 21(4): 187-90, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24479216

RESUMO

This study evaluated the colour stability of temporary prosthetic restorations with different thicknesses submitted to artificial accelerated aging. The occlusal surfaces of 40 molars were grinded to obtain flat enamel surfaces. Twenty acrylic resin specimens [Polymethyl methacrylate (Duralay) and Bis-methyl acrylate (Luxatemp)] were made with two different thicknesses, 0.5 mm and 1.0 mm. Temporary restorations were fixed on enamel and CIE L*a*b* colour parameters of each specimen were assessed before and after artificial accelerated aging. All groups showed colour alterations above the clinically acceptable limit. Luxatemp showed the lowest colour alteration regardless its thickness and Duralay showed the greatest alteration with 0.5 mm.


Assuntos
Materiais Dentários/química , Restauração Dentária Temporária , Metacrilatos/química , Condicionamento Ácido do Dente/métodos , Bis-Fenol A-Glicidil Metacrilato/química , Cor , Resinas Compostas/química , Colagem Dentária , Esmalte Dentário/anatomia & histologia , Polimento Dentário , Humanos , Teste de Materiais , Metilmetacrilatos/química , Polimerização , Polimetil Metacrilato/química , Cimentos de Resina/química , Propriedades de Superfície , Temperatura , Fatores de Tempo , Raios Ultravioleta
2.
Horm Metab Res ; 34(5): 260-4, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12063640

RESUMO

The IgG glycation level of 30 healthy subjects and 60 type 2 diabetic patients with different degrees of metabolic control was evaluated by matrix-assisted laser desorption ionization mass spectrometry, a technique allowing the determination of mass increase of the IgG molecule. When applied to the digested mixture obtained by the action of papain on the plasma protein fraction, the same method established the mass increase of Fab and Fc fragments of IgG; for the former, a higher mass increase was found, possibly explained by its high reactivity to glucose. Experimental results were confirmed by molecular modeling calculations. Results suggest that the immunodeficiency observed in diabetic patients may be due to the inhibition of molecular recognition between antibody and antigen as a result of a change in functionality of the modified Fab fragment of IgG.


Assuntos
Imunoglobulina G/metabolismo , Lisina/análogos & derivados , Idoso , Glicemia/metabolismo , Proteínas Sanguíneas/metabolismo , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Glucose/metabolismo , Hemoglobinas Glicadas/metabolismo , Glicoproteínas/metabolismo , Humanos , Fragmentos Fab das Imunoglobulinas/química , Fragmentos Fab das Imunoglobulinas/metabolismo , Imunoglobulina G/química , Lisina/sangue , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Proteínas/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
3.
J Am Soc Mass Spectrom ; 11(2): 153-9, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10689668

RESUMO

The glycation-induced functional change of immunoglobulins is of particular interest. The glycation levels of IgG in 10 healthy subjects and 20 diabetic patients with different degrees of metabolic control were studied by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. It reveals the number of glucose molecules that have condensed on the protein, which range from 1 to 5 for healthy subjects, from 5 to 9 for well controlled diabetic patients, and from 10 to 25 for poorly controlled ones. The identification of the most favored glycation sites has been obtained by MALDI analysis of standard and in vitro glycated IgG and plasma protein fraction of a healthy subject after digestion with papain, releasing Fab and Fc fragments of the molecule. Both experiments, as well as molecular modeling of the whole protein, confirm that the most of glucose molecules have condensed on the Fab fragment of IgG, suggesting that the immune deficiency observed in diabetic patients may be explained at the molecular level by a more effective glycation of the Fab fragment, thus inhibiting the process of molecular recognition between antibody and antigen.


Assuntos
Glucose/química , Imunoglobulina G/química , Idoso , Glicemia/metabolismo , Proteínas Sanguíneas/química , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hidrólise , Fragmentos Fab das Imunoglobulinas/química , Fragmentos Fc das Imunoglobulinas/química , Modelos Moleculares , Peso Molecular , Papaína , Conformação Proteica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
4.
Farmaco ; 50(3): 175-8, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7755864

RESUMO

The crystal structure of Cabergoline, a potent and long lasting prolactin lowering agent interacting with the D2 dopamine receptors, has been determined by X-ray diffraction data. The structural data represent the starting point for a computational study, where the molecular mechanisms approach was used to explore the motion of all unconstrained torsion angles. Two different conformations related to energetic minima have been found, one of them in agreement with the experimental crystal structure. Both conformations are shape compared with Bromocriptine and Lisuride, two dopaminergic ergoline derivatives with C-8 beta and C-8 alpha substituents of the ergoline ring, respectively. We observe that the C-8 beta Cabergoline assumes the overall three-dimensional features of C-8-alpha-ergolines in one of its low-energy conformations.


Assuntos
Bromocriptina/química , Agonistas de Dopamina/química , Ergolinas/química , Lisurida/química , Bromocriptina/farmacologia , Cabergolina , Cristalografia por Raios X , Agonistas de Dopamina/farmacologia , Ergolinas/farmacologia , Lisurida/farmacologia , Conformação Molecular , Relação Estrutura-Atividade
5.
J Med Chem ; 37(21): 3588-604, 1994 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-7932586

RESUMO

A new class of compounds combining thromboxane-A2 (TxA2) receptor antagonism and thromboxane synthase inhibition is described. A first series of (E)- and (Z)-[[[2-(1H-imidazol-1-yl)ethylidene]amino]oxy]pentanoic acids showed relevant thromboxane synthase inhibition associated with weak TxA2 receptor antagonism, while a series of (+/-)-(E)-[[[2-(1H-imidazol-1-yl)-3-phenylpropylidene]amino]oxy] pentanoic acids, structurally derived from the former, showed potent and well-balanced dual activity. Structural requirements for significant single and dual activity are discussed. Two close congeners of the latter series, (+/-)-(E)-5-[[[1-cyclohexyl-2-(1H-imidazol-1-yl)-3- phenylpropylidene]amino]oxy]pentanoic acid 23c and its p-fluorophenyl analog 23m, inhibited TxB2 production in vitro, in rat whole blood during clotting, with IC50 of 0.06 and 0.37 microM and antagonized the binding of [3H]SQ 29548 to washed human platelets, with IC50 of 0.08 and 0.02 microM, respectively. These two compounds were selected for further pharmacological evaluation and were shown to antagonize U46619-induced platelet aggregation in human platelet rich plasma with IC50 of 0.30 and 0.44 microM, respectively. They were both orally available, and in particular 23m caused a long lasting ex vivo TxA2 synthase inhibition in the fed rat. The levorotatory enantiomer of 23c, stereospecifically synthesized as a model compound, was found to be more potent than racemic 23c with regard to TxA2 receptor antagonism (IC50 = 0.04 microM) and equivalent to the latter with regard to TxA2 synthase inhibition. A molecular modeling study concerning the levorotatory enantiomer of 23c (S), TxA2, and representative TxA2 antagonists of different classes led to the definition of a putative pharmacophoric model for the TxA2 receptor ligands.


Assuntos
Imidazóis/síntese química , Ácidos Pentanoicos/síntese química , Receptores de Tromboxanos/antagonistas & inibidores , Tromboxano-A Sintase/antagonistas & inibidores , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico , Animais , Ligação Competitiva , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes , Simulação por Computador , Cães , Ácidos Graxos Insaturados , Fibrinolíticos , Humanos , Hidrazinas/sangue , Imidazóis/química , Imidazóis/farmacologia , Masculino , Modelos Moleculares , Estrutura Molecular , Ácidos Pentanoicos/química , Ácidos Pentanoicos/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Endoperóxidos Sintéticos de Prostaglandinas/farmacologia , Ratos , Ratos Sprague-Dawley , Estereoisomerismo , Tromboxano A2/análogos & derivados , Tromboxano A2/farmacologia , Tromboxano B2/antagonistas & inibidores
6.
J Med Chem ; 36(20): 2964-72, 1993 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-8411014

RESUMO

A series of derivatives of 4-phenyl-1,4-dihydropyridine bearing imidazol-1-yl or pyridin-3-yl moieties on the phenyl ring were synthesized with the aim of combining Ca2+ antagonism and thromboxane A2 (TxA2) synthase inhibition in the same molecule. Some of these compounds showed significant combined Ca2+ antagonism and TxA2 synthase inhibition in vitro, while others showed only one single activity. Structural requirements for significant single or combined activities are discussed. Theoretical conformational analysis, by molecular mechanics and semiempirical AM1 calculations, was performed for 1,4-dihydro-2,6-dimethyl-4-[3-(1H-imidazol-1-yl)phenyl]- 3,5-pyridinedicarboxylic acid, diethyl ester (FCE 24265) and two close congeners. FCE 24265, which inhibited TxB2 production in rat whole blood with IC50 = 1.7 x 10(-7) M and antagonized K+ induced contraction in guinea pig aorta with IC50 = 6.0 x 10(-8) M, was selected for further pharmacological evaluation. Our results show that this compound is less potent than nifedipine both in vitro and in vivo yet presents a favorable profile in vivo, lowering blood pressure without inducing reflex tachycardia. Moreover, its additional potent and selective TxA2 synthase inhibitory activity makes this compound an interesting pharmacologic tool in pathologies where both enhanced TxA2 synthesis and cellular Ca2+ overload are involved.


Assuntos
Cálcio/antagonistas & inibidores , Di-Hidropiridinas/síntese química , Imidazóis/síntese química , Piridinas/síntese química , Tromboxano-A Sintase/antagonistas & inibidores , Animais , Pressão Sanguínea/efeitos dos fármacos , Di-Hidropiridinas/farmacologia , Cães , Cobaias , Íleo/fisiologia , Imidazóis/farmacologia , Masculino , Estrutura Molecular , Contração Muscular/efeitos dos fármacos , Músculo Liso/fisiologia , Contração Miocárdica/efeitos dos fármacos , Nifedipino/farmacologia , Potássio/farmacologia , Piridinas/farmacologia , Coelhos , Ratos , Relação Estrutura-Atividade
7.
Mol Pharmacol ; 35(2): 251-6, 1989 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2918856

RESUMO

The comparative binding affinities for poly(dA-dT) and poly(dG-dC) of novel antitumor anthracyclines are reported. The data concern, besides the parent compound adriamycin (ADM), 4-demethoxy 6-deoxy 6-aminodaunomycin (II), 9-deoxy-ADM (III), 4-demethyl-6-O-methyl-ADM (IV), and 3'-deamino-3'-hydroxy-4'-epi-ADM (IV). Theoretical computations are performed in parallel for their comparative binding affinities to model double-stranded hexanucleotides, d(GCGCGC)2, d(TATATA)2, and d(CGTACG)2, using the SIBFA (sum of interactions between fragments computed ab inito) procedure. The computations reproduce in a very satisfactory manner the most salient features of the experimental comparative binding affinities. These encompass, in particular, a higher affinity for the d(TATATA)2 oligomer of II than that of ADM, despite the absence of the 14-OH substituent in II, a marked reversal of the CG versus TA sequence selectivity of the neutral compound V, favoring the d(CGCGCG)2 oligomer over the d(TATATA)2 one; and the deleterious effect incurred on the binding affinities by the presence of an O-methyl substituent at position 6 of the chromophore.


Assuntos
Antibióticos Antineoplásicos/metabolismo , DNA/metabolismo , Substâncias Intercalantes/metabolismo , Poli dA-dT/metabolismo , Polidesoxirribonucleotídeos/metabolismo , Relação Estrutura-Atividade
8.
Acta Crystallogr B ; 44 ( Pt 3): 307-15, 1988 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-3271110

RESUMO

(I): C19H22N4O2 (Registry No. 95688-34-9), m.p. greater than 573 K, Mr = 338.4, orthorhombic, P2(1)2(1)2(1), a = 8.392 (2), b = 13.004 (2), c = 15.676 (5) A, V = 1710.7 (7) A3, Z = 4, Dx = 1.31 Mg m-3, Mo Ka radiation, lambda = 0.71069 A, mu = 0.08 mm-1, F(000) = 720, T = 293 K, final R = 0.051 for 990 independent reflexions. (II): C26H33N3O3.1/2C7H8 (Registry No. 54370-23-9), m.p. 427-429 K, Mr = 481.64, monoclinic, P2(1), a = 11.595 (4), b = 14.274 (2), c = 16.103 (4) A, beta = 100.19 (3) degrees, V = 2623 (1) A3, Z = 4, Dx = 1.22 Mg m-3, Mo Ka radiation, lambda = 0.71069 A, mu = 0.07 mm-1, F(000) = 1036, T = 293 K, final R = 0.064 for 2738 independent reflexions. Two independent molecules constitute the asymmetric unit, together with a toluene molecule. Parallel investigations of the title compounds by single-crystal X-ray analysis and theoretical calculations have converged in showing an extended configuration of the side chain attached at the C8 atom of the ergoline nucleus.


Assuntos
Ergolinas , Difração de Raios X , Fenômenos Químicos , Físico-Química , Conformação Molecular
9.
J Comput Aided Mol Des ; 1(2): 121-32, 1987 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-3504212

RESUMO

Using computer-aided molecular modeling techniques to analyze models recently proposed for the receptor binding sites of dopaminergic agonists, we superimposed the chemical structures of various compounds that mimic the pharmacological behavior of dopamine, as well as inactive enantiomers, on a postulated three-dimensional frame of reference. We analyzed the vector directionalities of the lone pairs of the nitrogen common to these molecules, and the acidic hydrogen of phenols (in aminoindanes, aminotetralins, apomorphines, p-phenol-piperazines, octahydrobenzo(g)quinolines, octahydrobenzo(f)quinolines, and benzazepines) or of nitrogen (in ergoline-type compounds and related structures). This model, when expressed as distances from that of the reference compound pergolide, correlates with the dopaminergic binding affinity observed in compounds previously reported to act on the dopaniergic system in the central nervous system (CNS). The regression analysis of log KD with respect to the distances of the vectors of the acidic hydrogen support the hypothesis that these compounds bind to the receptor as donors in hydrogen bond formation.


Assuntos
Simulação por Computador , Dopamina , Desenho de Fármacos , Receptores Dopaminérgicos , Gráficos por Computador , Conformação Molecular , Relação Estrutura-Atividade , Termodinâmica
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