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Titolo:
REACTIONS OF A CISPLATIN ANALOG BEARING AN ESTROGENIC 1,2-DIARYLETHYLENEDIAMINE LIGAND WITH SULFUR-CONTAINING AMINO-ACIDS AND GLUTATHIONE
Autore:
BEDNARSKI PJ;
Indirizzi:
UNIV REGENSBURG,INST PHARM,LEHRSTUHL PHARMAZEUT CHEM 2 D-93040 REGENSBURG GERMANY
Titolo Testata:
Journal of inorganic biochemistry
fascicolo: 1, volume: 60, anno: 1995,
pagine: 1 - 19
SICI:
0162-0134(1995)60:1<1:ROACAB>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
CIS-DIAMMINEDIAQUAPLATINUM(II) CATION; PLATINUM COMPLEXES; METAL-COMPLEXES; CIS-DICHLORODIAMMINEPLATINUM(II); PHARMACOKINETICS; MECHANISMS; RESISTANCE; METHIONINE; INFUSION; BINDING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
41
Recensione:
Indirizzi per estratti:
Citazione:
P.J. Bednarski, "REACTIONS OF A CISPLATIN ANALOG BEARING AN ESTROGENIC 1,2-DIARYLETHYLENEDIAMINE LIGAND WITH SULFUR-CONTAINING AMINO-ACIDS AND GLUTATHIONE", Journal of inorganic biochemistry, 60(1), 1995, pp. 1-19

Abstract

The kinetics and the products of the reactions of the cisplatin analog hydroxyphenyl)ethylenediamine]dichloroplatinum(II) {[PtCl2(LL)]} with L-cysteine, D,L-homocysteine, L-methionine, and glutathione (GSH) were investigated by means of reversed-phase HPLC with diode-array UV-spectroscopic detection. The loss of [PtCl2(LL)] in the presence of nucleophile obeys the usual two-term rate law for substitution reactions with Pt(II); the values of the pseudo-first-order rate constants correspond to the hydrolysis rate constant for [PtCl2(LL)] (8.10+/-0.03) x 10(-5) sec(-1) at 37 degrees C. The value of the hydrolysis rate constant is independent of pH over a range of 2.8-8.3 at 37 degrees C. The values of the second-order rate constants for L-cysteine, D,L-homocysteine, L-methionine, and GSH are (2.34+/-0.37), (0.85+/-0.26), (3.74+/-0.60), and (1.13+/-0.17) x 10(-2)M(-1). sec(-1), respectively, at neutral pH and 37 degrees C. The reactivity of the thiol-containing nucleophiles increases with increasing pH; this effect is most pronounced with L-cysteine. At lower pH (i.e., 2.8) both L-cysteine and GSH react with [PtCl2(LL)] at rates comparable to the Pt-CI hydrolysis rate constant. The dependence of the rate constants on temperature was analyzed by Eyring plots: the Delta S-not equal values are negative for the reactions with H2O, GSH, and L-methionine, consistent with associative-type substitution reactions. Ail nucleophiles initially react with the Pt.-complex to form mono-adducts that have the diamine (LL) still chelated to platinum. In the case of the thiol-containing nucleophiles, however, the final product of these reactions is free LL. L-Methionine wasfound considerably less effective in causing the release of LL; the final products were identified by H-1-NMR to be diastereomeric monomethionine adducts, i.e., [Pt(LL)(Met-N,S)](+). The apparent rate of LL release is greatest with the sulfur-containing nucleophiles when the pH is maintained between 5.5 and 6.1. Diamine release slows moderately athigher pH (i.e., 7.9) and slows considerably at lower pH (i.e., 2.8).

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/10/20 alle ore 06:51:13