Linked Life Data

10907740

Source:http://linkedlifedata.com/resource/pubmed/id/10907740

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-10-3
pubmed:abstractText
Glutathione (GSH) reduction of the anticancer-active platinum(IV) compounds trans-[PtCl4(NH3)(thiazole)] (1), trans-[PtCl4(cha)(NH3)] (2), cis-[PtCl4(cha)(NH3)] (3) (cha=cyclohexylamine), and cis-[PtCl4(NH3)2] (4) has been investigated at 25 degrees C in a 1.0 M aqueous medium at pH 2.0-5.0 (1) and 4.5-6.8 (2-4) using stopped-flow spectrophotometry. The redox reactions follow the second-order rate law d[Pt(IV)]/dt=k[GSH]tot[Pt(IV)], where k is a pH-dependent rate constant and [GSH]tot the total concentration of glutathione. The reduction takes place via parallel reactions between the platinum(IV) complexes and the various protolytic species of glutathione. The pH dependence of the redox kinetics is ascribed to displacement of these protolytic equilibria. The thiolate species GS is the major reductant under the reaction conditions used. The second-order rate constants for reduction of compounds 1-4 by GS- are (1.43 +/- 0.01) x 10(7), (3.86 +/- 0.03) x 10(6), (1.83 +/- 0.01) x 10(6), and (1.18 +/- 0.01) x 10(6) M(-1)s(-1), respectively. Rate constants for reduction of 1 by the protonated species GSH are more than five orders of magnitude smaller. The mechanism for the reductive elimination reactions of the Pt(IV) compounds is proposed to involve an attack by glutathione on one of the mutually trans coordinated chloride ligands, leading to two-electron transfer via a chloride-bridged activated complex. The kinetics results together with literature data indicate that platinum(IV) complexes with a trans Cl-Pt-Cl axis are reduced rapidly by glutathione as well as by ascorbate. In agreement with this observation, cytotoxicity profiles for such complexes are very similar to those for the corresponding platinum(II) product complexes. The rapid reduction within 1 s of the platinum(IV) compounds with a trans Cl-Pt-C1 axis to their platinum(II) analogs does not seem to support the strategy of using kinetic inertness as a parameter to increase anticancer activity, at least for this class of compounds.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0949-8257
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
300-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Kinetics and mechanism for reduction of anticancer-active tetrachloroam(m)ine platinum(IV) compounds by glutathione.
pubmed:affiliation
Inorganic Chemistry 1, Chemical Center, Lund University, Lund, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't