Reaction kinetics of 4-methoxy ortho benzoquinone in relation to its mechanism of cytotoxicity: a pulse radiolysis study.
| dc.contributor.author | Land, Edward J | |
| dc.contributor.author | Cooksey, C J | |
| dc.contributor.author | Riley, P A | |
| dc.date.accessioned | 2010-08-17T13:40:53Z | |
| dc.date.available | 2010-08-17T13:40:53Z | |
| dc.date.issued | 1990-03-15 | |
| dc.identifier.citation | Reaction kinetics of 4-methoxy ortho benzoquinone in relation to its mechanism of cytotoxicity: a pulse radiolysis study. 1990, 39 (6):1133-5 Biochem. Pharmacol. | en |
| dc.identifier.issn | 0006-2952 | |
| dc.identifier.pmid | 2322299 | |
| dc.identifier.doi | 10.1016/0006-2952(90)90294-U | |
| dc.identifier.uri | http://hdl.handle.net/10541/109770 | |
| dc.description.abstract | Rate constants quantifying the reactivity of 4-methoxy ortho benzoquinone, formed in the metabolic activation of 4-hydroxyanisole, a possible melanocytotoxic drug under current assessment as a treatment for malignant melanoma, have been determined by pulse radiolysis. The quinone is reactive towards the thiols cysteine (k = 3.5x10(5)M-1sec-1), glutathione (k = 3.1x10(5)M-1sec-1) and dithiothreitol (k = 3.5x10(5)M-1sec-1), but relatively unreactive towards other nucleophiles such as arginine (k less than or equal to 1M-1sec-1) and glutamine (k less than or equal to 1M-1sec-1). Redox exchange with ascorbate also occurs (k = 1.0x10(4)M-1sec-1). In view of the low reactivity of 4-methoxy ortho benzosemiquinone towards oxygen (k less than or equal to 10(5)M-1sec-1) and the model lipid trans-2-butenoic acid (k less than or equal to 2x10(5)M-1sec-1), it is unlikely that initiation of lipid peroxidation by the semiquinone is a major source of cytotoxicity. A more likely toxicity pathway appears to be covalent addition reactions of 4-methoxy ortho benzoquinone with cellular nucleophiles, especially thiols, and/or redox exchange reactions of the quinone leading to antioxidant depletion. | |
| dc.language.iso | en | en |
| dc.subject | Anticancerous Agents | en |
| dc.subject.mesh | Antineoplastic Agents | |
| dc.subject.mesh | Benzoquinones | |
| dc.subject.mesh | Chemical Phenomena | |
| dc.subject.mesh | Chemistry | |
| dc.subject.mesh | Kinetics | |
| dc.subject.mesh | Oxidation-Reduction | |
| dc.subject.mesh | Pulse Radiolysis | |
| dc.subject.mesh | Quinones | |
| dc.title | Reaction kinetics of 4-methoxy ortho benzoquinone in relation to its mechanism of cytotoxicity: a pulse radiolysis study. | en |
| dc.type | Article | en |
| dc.contributor.department | Paterson Institute for Cancer Research, Christie Hospital and Holt Radium Institute, Manchester, U.K. | en |
| dc.identifier.journal | Biochemical Pharmacology | en |
| html.description.abstract | Rate constants quantifying the reactivity of 4-methoxy ortho benzoquinone, formed in the metabolic activation of 4-hydroxyanisole, a possible melanocytotoxic drug under current assessment as a treatment for malignant melanoma, have been determined by pulse radiolysis. The quinone is reactive towards the thiols cysteine (k = 3.5x10(5)M-1sec-1), glutathione (k = 3.1x10(5)M-1sec-1) and dithiothreitol (k = 3.5x10(5)M-1sec-1), but relatively unreactive towards other nucleophiles such as arginine (k less than or equal to 1M-1sec-1) and glutamine (k less than or equal to 1M-1sec-1). Redox exchange with ascorbate also occurs (k = 1.0x10(4)M-1sec-1). In view of the low reactivity of 4-methoxy ortho benzosemiquinone towards oxygen (k less than or equal to 10(5)M-1sec-1) and the model lipid trans-2-butenoic acid (k less than or equal to 2x10(5)M-1sec-1), it is unlikely that initiation of lipid peroxidation by the semiquinone is a major source of cytotoxicity. A more likely toxicity pathway appears to be covalent addition reactions of 4-methoxy ortho benzoquinone with cellular nucleophiles, especially thiols, and/or redox exchange reactions of the quinone leading to antioxidant depletion. |