Tyrosinase-mediated cytotoxicity of 4-substituted phenols: quantitative structure-thiol-reactivity relationships of the derived o-quinones.
Affiliation
Department of Chemistry, University College London, UK.Issue Date
1995-03
Metadata
Show full item recordAbstract
Rate constants have been determined for reactions between biologically significant thiols, represented by cysteine and glutathione, and a series of 10 4-substituted o-quinones, and unsubstituted o-quinone itself, generated by rapid disproportionation of the semiquinones formed from the corresponding catechols by pulse radiolysis. The quantitative structure-reactivity relationships were investigated by examining the correlation between the rate constants and various Hammett and other parameters characterizing the electronic nature of the substituents. From these relationships, it can be concluded that the o-quinone reactivity with thiols increases with the electron-withdrawing capacity of the substituent groups and that this effect is principally due to resonance effects. Such relationships allow the prediction of likely reactivities with cellular thiols of further o-quinones whose 4-substituents have known electronic parameters. These reactivities are likely to be one of the critical factors determining overall cytotoxicity, assisting in the choice of improved melanogenesis-targeted anti-melanoma drugs.Citation
Tyrosinase-mediated cytotoxicity of 4-substituted phenols: quantitative structure-thiol-reactivity relationships of the derived o-quinones. 1995, 10 (2):119-29 Anticancer Drug Des.Journal
Anti-Cancer Drug DesignPubMed ID
7710634Type
ArticleLanguage
enISSN
0266-9536Collections
Related articles
- Reactivity of orthoquinones involved in tyrosinase-dependent cytotoxicity: differences between alkylthio- and alkoxy-substituents.
- Authors: Cooksey CJ, Jimbow K, Land EJ, Riley PA
- Issue date: 1992 Dec
- Chemical Reactivities of ortho-Quinones Produced in Living Organisms: Fate of Quinonoid Products Formed by Tyrosinase and Phenoloxidase Action on Phenols and Catechols.
- Authors: Ito S, Sugumaran M, Wakamatsu K
- Issue date: 2020 Aug 24
- Melanogenesis-targeted anti-melanoma pro-drug development: effect of side-chain variations on the cytotoxicity of tyrosinase-generated ortho-quinones in a model screening system.
- Authors: Riley PA, Cooksey CJ, Johnson CI, Land EJ, Latter AM, Ramsden CA
- Issue date: 1997 Jan
- Quinone chemistry and melanogenesis.
- Authors: Land EJ, Ramsden CA, Riley PA
- Issue date: 2004
- The reactivity of o-quinones which do not isomerize to quinone methides correlates with alkylcatechol-induced toxicity in human melanoma cells.
- Authors: Bolton JL, Pisha E, Shen L, Krol ES, Iverson SL, Huang Z, van Breemen RB, Pezzuto JM
- Issue date: 1997 Sep 12