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1.
Science ; 216(4549): 982-4, 1982 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-17809067

RESUMO

A new carotenoporphyrin has been prepared in which a synthetic carotenoid is joined to a tetraarylporphyrin through a flexible trimethylene linkage. This molecule exists primarily in an extended conformation with the carotenoid chromophore far from the porphyrin pi-electron system. In benzene solution, where large-amplitude molecular motions are rapid, the molecule can momentarily assume less stable conformations which favor triplet energy transfer, and quenching of the porphyrin triplet by the carotenoid is fast. In a polystyrene matrix or frozen glass such motions are slow, and energy transfer cannot compete with other pathways for depopulating the triplet state. These observations help establish the requirements for biological photoprotection.

2.
Free Radic Biol Med ; 28(11): 1638-41, 2000 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-10938460

RESUMO

Using semi-empirical AM1 calculation and 6.31G* basis sets, we have calculated the energy of the highest-occupied molecular orbital (E(HOMO)) for anti-inflammatory 4,5-diarylpyrroles which have been shown to have inhibitory activity on cyclooxygenase COX-2, an inducible enzyme expressed during inflammation. We have found a correlation between the E(HOMO) of a molecule and its COX-2 inhibition. However, no correlation was observed between E(HOMO) and the inhibition efficiency of cyclooxygenase-1 (COX-1), the constitutively expressed enzyme, protective to the organism. This result suggests that the inhibitions of the two isoforms follow different molecular mechanisms.


Assuntos
Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Isoenzimas/antagonistas & inibidores , Pirróis/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Técnicas In Vitro , Isoenzimas/farmacologia , Oxirredução , Prostaglandina-Endoperóxido Sintases/farmacologia , Pirróis/química , Relação Estrutura-Atividade , Termodinâmica
3.
Free Radic Biol Med ; 26(9-10): 1261-6, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10381198

RESUMO

Using a simple quantum mechanical method, we calculated the energy of the highest-occupied molecular orbital (E(HOMO)) of three groups of anti-inflammatory compounds, and we have found correlations between E(HOMO) of these molecules and experimental data previously reported on (1) inhibition of sheep-vesicular-gland prostaglandin cyclooxygenase by phenolic compounds, (2) inhibition of prostaglandin cyclooxygenase in mouse macrophages by salicylates, benzoates and phenols, and (3) peroxyl-radical scavenging and radioprotection of a bacterial virus by NSAID drugs, including metiazinic acid, sulindac, D-penicillamine, piroxicam, indomethacin, benoxaprofen, and aspirin. Our correlations using a systematic evaluation of the HOMO energies can be of predictive value in the search for new anti-inflammatory drugs as well as for new radioprotectors.


Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Animais , Bacteriófagos/efeitos dos fármacos , Bacteriófagos/efeitos da radiação , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Técnicas In Vitro , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Camundongos , Modelos Químicos , Teoria Quântica , Ovinos , Relação Estrutura-Atividade , Termodinâmica
4.
Free Radic Biol Med ; 27(1-2): 95-9, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10443925

RESUMO

The purpose of the present work has been to seek a correlation of potential predictive value, demonstrating redox control of cytotoxicity toward human nasopharynx carcinoma (KB) cells by seven 5-hydroxy-7-methoxyflavones, together with two glycoside derivatives, all extracted from Lethedon tannaensis. In this approach, redox control is characterized by a physicochemical parameter expressing quantitatively the relative electron-donating power of the flavones, this parameter being the second order rate constant, kdelta, for quenching of singlet oxygen O2 (1deltag). This rate constant kdelta is usually related to the ability of a given molecule D to donate an electron and, thus, with the reduction potential E of the couple (D*+/D). Our results show that the flavone toxicity is linearly correlated with ease of oxidation: the higher the rate constant of reaction with singlet oxygen, the easier the oxidation, the less positive or more negative the reduction potential ((D*+/D), the higher the cytotoxicity. The results suggest new screening strategies to identify and improve potential antitumor drugs.


Assuntos
Antineoplásicos Fitogênicos/metabolismo , Flavonoides/metabolismo , Plantas Medicinais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Humanos , Estrutura Molecular , Oxirredução , Células Tumorais Cultivadas
5.
Free Radic Biol Med ; 29(1): 26-33, 2000 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-10962202

RESUMO

Using pulse radiolysis and laser flash photolysis, we have investigated the reactions of the deleterious species, e(-)(aq), HO&z.rad;, O(2)(*)(-) and O(2)((1)Delta(g)) with 10 water-soluble cyclopropyl-fused C(60) derivatives including a mono-adduct dendro[60]fullerene (d) and C(60) derivatives based on C(60)[C(COOH)(2)](n=2-6), some of which are known to be neuroprotective in vivo. The rate constants for reactions of e(-)(aq) and HO&z.rad; lie in the range 0.5-3.3 x 10(10) M(-1) s(-1). The d and bis-adduct monoanion radicals display sharp absorption peaks around 1000 nm (epsilon = 7 000-11 500 M(-1) cm(-1)); the anions of the tris-, tetra-, and penta-adduct derivatives have broader, weaker absorptions. The monohydroxylated radicals have their most intense absorption maxima around 390-440 nm (epsilon = 1000-3000 M(-1) cm(-1)). The anion and hydroxylated radical absorption spectra display a blue-shift as the number of addends increases. The radical anions react with oxygen (k approximately 10(7)-10(9) M(-1) s(-1)). The reaction of O(2)(*)(-) with the C(60) derivatives does not occur via an electron transfer. The rate constants for singlet oxygen reaction with the dendrofullerene and eee-derivative in D(2)O at pH 7.4 are k approximately 7 x 10(7) and approximately 2 x 10(7) M(-1) s(-1) respectively, in contrast to approximately 1.2 x 10(5) M(-1) s(-1) for the reaction with C(60) in C(6)D(6). The large acceleration of the rates for electron reduction and singlet oxygen reactions in water is due to a solvophobic process.


Assuntos
Carbono/química , Radicais Livres/química , Fulerenos , Radical Hidroxila/química , Oxigênio/química , Modelos Moleculares , Fotólise , Radiólise de Impulso , Relação Estrutura-Atividade
6.
Curr Pharm Des ; 7(17): 1781-821, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11562310

RESUMO

This review describes recent advances in the development of DNA-photocleavage agents. Major mechanisms of photosensitized DNA photocleavage are presented and the most popular categories of compounds are considered, which include metal complexes and many organic functional derivatives. DNA-targeted conjugates of photosensitizers are also described and discussed.


Assuntos
Dano ao DNA , DNA/metabolismo , Fármacos Fotossensibilizantes/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Sequência de Bases/efeitos dos fármacos , Sítios de Ligação/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Fotoquímica
7.
Chemphyschem ; 2(2): 109-14, 2001 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-23696436

RESUMO

The particular chromophoric structure of C(70)Ph(10), which consists of two cage-centered π-electron systems, makes its photophysical properties an exception to those found for other phenylated [70]fullerenes C(70)Ph(2n) (n=2-4). For these other C(70)Ph(2n) species, their intrinsic photophysical properties undergo smooth transitions as a function of n.


Assuntos
Fulerenos/química , Teoria Quântica , Benzeno/química , Espectrofotometria Ultravioleta , Estereoisomerismo
8.
Photochem Photobiol ; 54(5): 733-6, 1991 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1798750

RESUMO

The bimolecular rate constants (k) of quenching of molecular singlet oxygen 1O2 (1 delta g) by organo-selenium compounds exhibiting glutathione peroxidase activity and by sulfur analogs have been determined by time resolved phosphorescence detection of 1O2 in CD3OD and C6D6, with no solvent effect. The rate constants of quenching by the Se-containing compounds were found to be approximately one order of magnitude higher than those of the S-containing homologs. A linear correlation was observed between log k and the Hammett constant omega ortho with p = -0.89, the rate constant being higher for molecules with an electron-donating substituent and lower for those with an electron-withdrawing substituent. This observation is consistent with the involvement of a charge transfer complex in the deactivation of singlet oxygen.


Assuntos
Antioxidantes/química , Azóis/química , Compostos Organosselênicos/química , Oxigênio/química , Fotoquímica , Protetores contra Radiação/química , Glutationa Peroxidase , Isoindóis , Cinética , Luminescência , Enxofre/química
9.
Photochem Photobiol ; 50(3): 321-5, 1989 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2780822

RESUMO

The rate constants of molecular singlet oxygen quenching by saturated and unsaturated fatty-acids and by cholesterol-membrane critical components - membrane critical components - have been measured by time resolved detection of the 1270 nm phosphorescence of singlet molecular oxygen [O2(1deltag)]. We have determined (i) an increment of 5.7 x 10(2)M(-1)s(-1) per -CH2- in C6D6 and CD3OD for saturated fatty acids between C4 and C20, (ii) an increment of 3 x 10(4)M(-1)s(-1) per non-conjugated cis-double bond for C18 unsaturated fatty acids, identical in C6D6 and DC3OD, (iii) a lower quenching rate constant by a factor of 2.7 for the trans-C16 and trans-C18 as compared to the corresponding cis-monounsaturated fatty acids, (iv) a rate constant of O2x(1deltag) quenching by cholesterol of 5.7 x 10(4)M(-1)s(-1) in benzene. These rate constants are compared to those obtained for other membrane cellular components.


Assuntos
Colesterol , Ácidos Graxos , Oxigênio , Ácidos Graxos Insaturados , Fotoquímica , Relação Estrutura-Atividade
10.
Photochem Photobiol ; 51(6): 635-41, 1990 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2367560

RESUMO

The quantum yield of triplet formation, phi T, and that of the photosensitized formation of singlet molecular oxygen, phi delta, were determined for a rare nucleoside, 4-thiouridine (4t-Urd), in water and in acetonitrile, using singlet molecular oxygen phosphorescence, laser-induced optoacoustics and time-resolved thermal lensing. These yields, phi T and phi delta, the latter in aerated solutions, were found to be, respectively, in water: 0.67 +/- 0.17 and 0.18 +/- 0.04 and in acetonitrile: 0.61 +/- 0.15 and 0.50 +/- 0.20. The fraction of the 4t-Urd triplet molecules quenched by oxygen leading to singlet molecular oxygen, S delta, was calculated to be between 0.7 and unity in both solvents, this value being indicative of a pi pi*character for the lowest triplet state of 4t-Urd.


Assuntos
Oxigênio , Tiouridina , Acetonitrilas , Luminescência , Fotoquímica , Teoria Quântica , Oxigênio Singlete , Água
11.
Photochem Photobiol ; 51(4): 419-26, 1990 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2343060

RESUMO

Tetraarylporphyrins substituted with nitro groups at beta-pyrrolic positions are potential candidates for electron-accepting pigments in model systems for photosynthesis. The photophysics of 2-nitro-5,10,15,20-tetra-p-tolylporphyrin and its zinc analog have been studied in order to evaluate this potential. The ground state absorption spectrum, the triplet-triplet absorption spectrum, the fluorescence emission spectrum, and associated photophysical parameters have been determined. The molecules have short singlet lifetimes and anomalous temperature- and solvent-dependent emission spectra which are consistent with the formation of an intramolecular charge transfer state of the type P+.-NO2-. in which the nitro group is twisted about its bond to the porphyrin, relative to the ground state conformation.


Assuntos
Nitrocompostos/síntese química , Porfirinas/síntese química , Radiossensibilizantes/síntese química , Estrutura Molecular , Espectrometria de Fluorescência , Espectrofotometria , Relação Estrutura-Atividade
17.
C R Acad Sci III ; 307(18): 807-10, 1988.
Artigo em Francês | MEDLINE | ID: mdl-3146411

RESUMO

Prooxidant states, characterised by an increase in the intracellular concentration of activated forms of oxygen, are able to promote tumors. The inhibitory effects of synthetic phenolic compounds added to the diet of mice on benzo(a)pyrene-induced neoplasia of the forestomach have been determined by Wattenberg et al. The efficiency of this inhibition has been estimated quantitatively for each phenol, using the ratio R of the number of tumors per mouse in the treated group over the number of tumors per mouse in the control group. We have observed a linear correlation between the antitumoral efficiency (1-R) and the logarithm of the rate of quenching of singlet oxygen, k, y, by this family of phenols, log k being itself correlated with the half-wave oxidation potential of the phenols. These correlations suggest a charge transfer mechanism for the inhibition of neoplasia induced by benzo(a)pyrene, B(a)P. It should be pointed out that singlet oxygen can be generated via enzymatic reactions in the dark and thus might play a role in the formation of the ultimate carcinogenic metabolite B(a)P-7, 8-dihydroxy-9, 10-epoxide. The correlations described emphasize the interest in scaling the inhibitors of mutagenicity induced by polycyclic aromatic hydrocarbons with respect to their oxidation potentials. Our result is a first step towards a better understanding of the molecular reactions involved in chemically-induced neoplasia and in its prevention.


Assuntos
Benzo(a)pireno , Neoplasias Experimentais/prevenção & controle , Oxigênio/antagonistas & inibidores , Fenóis/farmacologia , Animais , Camundongos , Neoplasias Experimentais/induzido quimicamente , Oxirredução , Fenóis/uso terapêutico , Oxigênio Singlete
18.
Free Radic Res Commun ; 8(4-6): 251-8, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2354806

RESUMO

The inhibitory effects of synthetic phenolic compounds on benzo(a)pyrene-induced neoplasia of the mouse forestomach have been measured by Wattenberg et al. The efficiency of this inhibition has been estimated for each phenol, using R, the ratio of the number of tumors per mouse in the protected group over the number of tumours per mouse in the control group. We have observed a linear correlation between the chemoprotection efficiency R and the logarithm of the rate of quenching of singlet oxygen, k, by this family of phenols, log k being itself correlated with the one-electron oxidation potential of the phenols. These correlations suggest a charge transfer mechanism for the inhibition of neoplasia induced by benzo(a)pyrene. The correlations described provide a theoretical basis for scaling the inhibitors of mutagenicity induced by polycyclic aromatic compounds in terms of their oxidation potentials.


Assuntos
Antineoplásicos , Neoplasias Experimentais/tratamento farmacológico , Fenóis/análise , Animais , Antioxidantes/farmacologia , Benzo(a)pireno , Soluções Tampão , Eletroquímica , Hematoporfirinas/análise , Camundongos , Neoplasias Experimentais/induzido quimicamente , Oxirredução , Oxigênio/análise , Fenóis/farmacologia , Radiólise de Impulso
19.
Biochemistry ; 26(11): 3087-92, 1987 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-3607012

RESUMO

The linear dichroism spectra of complexes of tetrakis(N-methyl-4-pyridinio)prophine (H2TMpyP) and its zinc(II) derivative (ZnTMpyP) with DNA oriented in a flow gradient have been investigated. The dichroism of H2TMpyP determined within the Soret band and the Qy band system is consistent with an intercalative conformation in which the plane of the porphyrin ring system is nearly parallel to the planes of the DNA bases. In the case of ZnTMpyP on the other hand, the porphyrin ring system is inclined at angles of 62-67 degrees with respect to the axis of the DNA helix. The pyridyl groups in both cases are characterized by a low degree of orientation with respect to the axis of the helix. In contrast to H2TMpyP which does not significantly affect the degree of alignment of the DNA in the flow gradient, the binding of ZnTMpyP causes a significant decrease (about 50% for a base pair/ZnTMpyP ratio of 20) in the intrinsic dichroism at 260 nm due to the oriented DNA bases; the binding of ZnTMpyP to DNA either gives rise to regions of higher flexibility or causes bends or kinks at the binding sites. Increasing the ionic strength has little influence on the linear dichroism of the ZnTMpyP-DNA complexes, but the number of molecules bound at intercalation sites diminishes in the case of the H2TMpyP-DNA complexes; the accompanying changes in the linear dichroism characteristics suggest that external H2TMpyP complexes are formed at the expense of intercalation complexes.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
DNA , Porfirinas , Substâncias Intercalantes , Conformação de Ácido Nucleico , Oxirredução , Espectrofotometria/métodos
20.
Mol Pharmacol ; 42(4): 718-22, 1992 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1435748

RESUMO

The second-order rate constants, k delta, for quenching of molecular singlet oxygen O2 (1 delta g) by nonsteroidal anti-inflammatory imidazole drugs have been determined using time-resolved phosphorescence detection of singlet oxygen. A linear correlation was observed between log k delta (ranging from 7.90 to 8.50) and the anti-inflammatory activity of these compounds (ranging from ED50 = 15 to 300 mg/kg), as measured in rats by Jørgensen and Dyrsting [United States Patent 4,424,229 (1984)]. The correlation between this physico-chemical parameter measured in vitro and a biological activity measured in vivo might be useful in screening other types of candidate anti-inflammatory drugs. The rate constant (k delta) can be considered as a quantitative expression of the electron-donating power of the imidazole drug, as suggested by a correlation of log k deta (ranging from 6.02 to 7.45) with Hammett substituent parameters observed in the case of 2-substituted imidazoles.


Assuntos
Anti-Inflamatórios não Esteroides/química , Imidazóis/química , Oxigênio/química , Animais , Anti-Inflamatórios , Flúor/química , Ratos , Relação Estrutura-Atividade
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