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Titolo:
UNUSUAL REACTIVITY OF CISPLATIN ANALOGS THAT BEAR O-PHENYLENEDIAMINE LIGANDS - INSIGHTS FOR THE DESIGN OF MORE EFFECTIVE CYTOTOXIC AGENTS
Autore:
KOCKERBAUER R; BEDNARSKI PJ;
Indirizzi:
UNIV REGENSBURG,LEHRSTUHL PHARMAZEUT CHEM 2,INST PHARM D-93040 REGENSBURG GERMANY UNIV REGENSBURG,LEHRSTUHL PHARMAZEUT CHEM 2,INST PHARM D-93040 REGENSBURG GERMANY
Titolo Testata:
Journal of inorganic biochemistry
fascicolo: 4, volume: 62, anno: 1996,
pagine: 281 - 298
SICI:
0162-0134(1996)62:4<281:UROCAT>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
MIXED-AMINE CISPLATIN; AQUEOUS CHEMISTRY; COMPLEXES; METABOLITES; METHIONINE; INVITRO;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
29
Recensione:
Indirizzi per estratti:
Citazione:
R. Kockerbauer e P.J. Bednarski, "UNUSUAL REACTIVITY OF CISPLATIN ANALOGS THAT BEAR O-PHENYLENEDIAMINE LIGANDS - INSIGHTS FOR THE DESIGN OF MORE EFFECTIVE CYTOTOXIC AGENTS", Journal of inorganic biochemistry, 62(4), 1996, pp. 281-298

Abstract

The stabilities of dichloro(o-phenylenediamine)platinum(II) (1) and several 4,5-disubstituted analogs [i.e., with: Cl (2), Br (3), Me (4), or MeO (5)] were investigated under various aqueous conditions. The Ptcomplexes 1-5 decomposed by reactions which were independent of the amount of chloride in the medium. The poor aqueous stabilities of 1-5 were attributed to two factors: 1) The compounds underwent facile oxidation reactions in aqueous solution at pH 7.4 and 37 degrees C, resulting in the formation of intensely colored Pt-species as well as H2O2. Compounds 2 and 3 oxidized considerably faster than 1, 4, and 5. Based on the redox behavior and UV-Vis spectra of the decomposition products, it is proposed that they are o-benzoquinonediimine Pt complexes. 2) Compound 4 underwent an unusually rapid substitution reaction with L-methionine, a component of the culture medium, whereby both of the chloro ligands of platinum were replaced by an N,S-chelated methionine. Atan L-methionine concentration of 0.5 mM, the reaction ran to completion within 1 min. Thus, the weak growth inhibitory activities of 1-5 onhuman cancer cells in vitro was likely a result of their poor chemical stability in the culture medium. Based on a knowledge of the decomposition pathways, analogs were designed to be resistant to these types of reactions. Dichloro(o-aminomethylaniline)platinum(II) (6) and [bis-1,2(aminomethyl)benzene]-dichloroplatinum(II) (7) were synthesized andtheir aqueous stabilities investigated. Both 6 and 7 were considerably more stable than 1-5 under aqueous conditions, as well as being moreeffective in inhibiting the growth of human cancer cells in vitro.

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Documento generato il 24/10/20 alle ore 14:45:50