4-Substituted 1-chloo-2-nitrobenzenes: Structure-activity relationships and extension of the subrate model of rat glutathione S-transferase 4-4.

E.M. van der Aar, M.J. de Groot, T. Bouwman, G.J. Bijlo, J.N.M. Commandeur, N.P.E. Vermeulen

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In the present study, eleven 4-substituted 1-chloro-2-nitrobenzenes were tested for their GSH conjugation capacity when catalyzed by base or rat glutathione S-transferase (GST) 4-4. Kinetic parameters (k(s) and K(m), k(cat), and k(cat)/K(m)) were determined and subsequently used for the description of structure-activity relationships (SAR's). For this purpose, eight physicochemical parameters (electronic, steric, and lipophilic) of the substituents and five computer-calculated parameters of the substrates (charge distributions and several energy values) were used in regression analyses with the kinetic parameters. The obtained SAR's are compared with corresponding SAR's for the GSH conjugation of 2-substituted 1-chloro-4- nitrobenzenes, previously determined [Van der Aar et al. (1996) Chem. Res. Toxicol. 9, 527-534]. The kinetic parameters of the 4-substituted 1-chloro- 2-nitrobenzenes correlated well with the Hammett σ(p)
Original languageEnglish
Pages (from-to)439-449
JournalChemical Research in Toxicology
Publication statusPublished - 1997


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