Tyrosinase-mediated cytotoxicity of 4-substituted phenols: quantitative structure-thiol-reactivity relationships of the derived o-quinones.
AffiliationDepartment of Chemistry, University College London, UK.
MetadataShow full item record
AbstractRate 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.
CitationTyrosinase-mediated cytotoxicity of 4-substituted phenols: quantitative structure-thiol-reactivity relationships of the derived o-quinones. 1995, 10 (2):119-29 Anticancer Drug Des.
JournalAnti-Cancer Drug Design
- 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
- 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
- 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
- Oxidation of 4-alkylphenols and catechols by tyrosinase: ortho-substituents alter the mechanism of quinoid formation.
- Authors: Krol ES, Bolton JL
- Issue date: 1997 Apr 18
- Polycyclic aromatic hydrocarbon (PAH) ortho-quinone conjugate chemistry: kinetics of thiol addition to PAH ortho-quinones and structures of thioether adducts of naphthalene-1,2-dione.
- Authors: Murty VS, Penning TM
- Issue date: 1992 Sep 28