In vitro studies on DNA-photosensitization by different drug stereoisomers

Lhiaubet‐Vallet, Virginie; Sarabia, Zaideth; Hernández, Daniel E.; Castell, José V.; Miranda, Miguel A.

doi:10.1016/s0887-2333(03)00108-5

Cited by 16 publications

(21 citation statements)

References 14 publications

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“…[34] Carprofen, like the main photoproduct formed in this process (PP), [35] can also undergo photodecarboxylation as a minor reaction pathway. Although DNA photosensitization by CP has been investigated, [36] no study concerning the potential interactions of its photoproducts with DNA has yet been realized.…”

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confidence: 99%

Model Studies on a Carprofen Derivative as Dual Photosensitizer for Thymine Dimerization and (6–4) Photoproduct Repair

et al. 2007

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Cyclobutane pyrimidine dimers (CPD) and (6-4) photoproducts are among the main UV-induced DNA lesions. Both types of damage are mostly repaired in prokaryotes by photolyase enzymes. The repair mechanism of (6-4) photolyases has still not been fully elucidated, but it is assumed that back rearrangement to the oxetane occurs prior to repair. In this work, a non-steroidal anti-inflammatory drug derivative corresponding to the dechlorinated methyl ester of carprofen (namely methyl 2-(carbazol-2-yl)propanoate, PPMe) has been used to achieve the photosensitized cycloreversion of model oxetanes (formally resulting from photocycloaddition between benzophenone and 1,3-dimethylthymine or 2'-deoxyuridine), by employing fluorescence spectroscopy, laser flash photolysis, HPLC and NMR. Although PPMe is able to photoinduce the cycloreversion of both oxetanes, the fluorescence quenching of PPMe is faster for the 2'-deoxyribose-containing oxetane; this underlines the importance of the structure in such studies. Moreover, PPMe was shown to photoinduce the formation of thymidine cyclobutane dimers through a triplet-triplet energy transfer from a vibrationally excited state, as suggested by the enhanced PPMe triplet quenching by thymidine with increasing temperature. These results reveal a dual role of PPMe in DNA photosensitization, in that it photoinduces either damage or repair.

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confidence: 99%

Model Studies on a Carprofen Derivative as Dual Photosensitizer for Thymine Dimerization and (6–4) Photoproduct Repair

et al. 2007

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“…Soc. 1072 biomolecules [18][19][20][21] and, for the DNA case, this process can be responsible for photogenotoxicity. [22][23][24][25] Of special importance is the effect of triplet carbonyl compounds on the photoxidative process of tyrosine and tryptophan, nucleic acid constituents containing a phenol or an indole group, respectively, since this type of reaction can result in high photoallergic activity when several drugs containing the carbonyl group are employed.…”

Section: Introductionmentioning

confidence: 99%

“…17 This photosensitization process involves direct interaction between the triplet excited state of the sensitizer (the triplet carbonyl) and the biological substrate through the formation of an encounter complex. This species leads to an electron transfer reaction followed by a proton transfer, resulting in the formation of the corresponding radical pair sensitizer/ biological substrate with the consequent damage of several biomolecules [18][19][20][21] and, for the DNA case, this process can be responsible for photogenotoxicity. [22][23][24][25] Of special importance is the effect of triplet carbonyl compounds on the photoxidative process of tyrosine and tryptophan, nucleic acid constituents containing a phenol or an indole group, respectively, since this type of reaction can result in high photoallergic activity when several drugs containing the carbonyl group are employed.…”

Section: Introductionmentioning

confidence: 99%

Phenolic hydrogen abstraction by the triplet excited state of thiochromanone: a laser flash photolysis study

Ribeiro¹,

Bertoti²,

Netto‐Ferreira³

2010

J. Braz. Chem. Soc.

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O estado excitado triplete de cetonas pode oxidar substratos biológicos acarretando danos a diversas biomoléculas como aminoácidos, nucleosídeos e mesmo DNA. Como parte de nossos estudos acerca da interação entre carbonilas e fenóis, foi investigada a reatividade do estado excitado triplete de tiocromanona (1) frente a fenóis, em acetonitrila, empregando a técnica de fotólise por pulso de laser de nanossegundo. As constantes de velocidade de supressão obtidas variaram de (1,1 ± 0,1) × 10 8 L mol -1 s -1 (4-cianofenol) a (5,8 ± 1,0) × 10 9 L mol -1 s -1 (hidroquinona). Um gráfico de Hammett para a reação do triplete de 1 com uma série de fenóis contendo substituintes polares resultou em uma constante de reação r = -0,90. Este valor negativo para a constante de reação r está plenamente de acordo com um mecanismo envolvendo uma transferência acoplada elétron/ próton no processo de transferência de hidrogênio do fenol para a carbonila triplete.Triplet ketones are known to oxidize biological substrates which can lead to damage of several biomolecules such as amino acids, nucleosides and DNA. As part of our systematic study on the interaction between carbonyl compounds and phenols, the triplet reactivity of thiochromanone (1) towards substituted phenols, in acetonitrile, was investigated employing the laser flash photolysis technique. The quenching rate constants ranged from (1.1 ± 0.1) × 10 8 L mol -1 s -1 (4-cyanophenol) to (5.8 ± 1.0) × 10 9 L mol -1 s -1 (hydroquinone). A Hammett plot for the reaction of triplet 1 with phenols containing polar substituents resulted in a reaction constant r = -0.90. This negative value observed for the reaction constant r is in accord with a mechanism in which the hydrogen transfer from phenols to the triplet carbonyl involves a coupled electron/proton transfer.Keywords: thiochromanone, laser flash photolysis, triplet excited state, hydrogen donors IntroductionIn the last few years the phenolic hydrogen abstraction by carbonyl compounds in the triplet excited state has been extensively studied employing experimental and theoretical methods. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] The mechanism for this process is now well established and involves the initial formation of a hydrogen-bonded exciplex in the triplet excited state, followed by electron transfer and, subsequently, an ultrafast proton transfer. 4,9-16 DFT calculations clearly showed that for the triplet complex (exciplex) ketone-phenol the hydrogen transfer is predominantly occurring. 8 The very fast quenching rate constants of triplet carbonyls towards phenols is consequence of both the low reduction potential of the former as well as the low oxidation potential of the later. 4,16 Experimentally, this coupled electron/proton transfer mechanism ultimately results in the formation of the ketyl-aryloxyl radical pair.Triplet ketones are known to oxidize biological substrates such as amino acids, nucleosides and DNA. Due to this, topical or systemic administration of drugs containing the carbonyl chromophore c...

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“…Most of them are based on highperformance liquid chromatography (HPLC) and are used to determine the levels of FQs in human plasma [4][5][6][7]. Because the clinical use of FQs is somewhat limited by the development of photosensitivity, central nervous system injuries, or DNA photosensitization [3,[8][9][10][11][12], it is important to be aware of the risk factors that might lead to a greater incidence of such damage. One mechanism through which FQs induce toxicity is believed to involve the generation of reactive oxygen radical species [13][14][15], which have the main effect of altering the balance in oxidant/antioxidant systems and, subsequently, inducing oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of malondialdehyde and ofloxacin in plasma using an isocratic high-performance liquid chromatography/fluorescence detection system

Cheng

Huang

2008

Analytica Chimica Acta

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In vitro studies on DNA-photosensitization by different drug stereoisomers

Cited by 16 publications

References 14 publications

Model Studies on a Carprofen Derivative as Dual Photosensitizer for Thymine Dimerization and (6–4) Photoproduct Repair

Model Studies on a Carprofen Derivative as Dual Photosensitizer for Thymine Dimerization and (6–4) Photoproduct Repair

Phenolic hydrogen abstraction by the triplet excited state of thiochromanone: a laser flash photolysis study

Simultaneous determination of malondialdehyde and ofloxacin in plasma using an isocratic high-performance liquid chromatography/fluorescence detection system

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