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Titolo:
CHELATE-RING-OPENED ADDUCTS OF [PT(EN)(ME-MAL-O,O')] (EN EQUALS ETHANE-1,2-DIAMINE, ME-MAL EQUALS 2-METHYLMALONATE) WITH METHIONINE DERIVATIVES - RELEVANCE TO THE BIOLOGICAL-ACTIVITY OF PLATINUM ANTICANCER AGENTS
Autore:
GUO ZJ; HAMBLEY TW; MURDOCH PD; SADLER PJ; FREY U;
Indirizzi:
UNIV EDINBURGH,DEPT CHEM,W MAINS RD,KINGS BLDG EDINBURGH EH9 3JJ MIDLOTHIAN SCOTLAND UNIV LONDON,BIRKBECK COLL,DEPT CHEM LONDON WC1H 0PP ENGLAND UNIV LAUSANNE,BCH,INST CHIM MINERALE & ANALYT CH-1015 LAUSANNE SWITZERLAND
Titolo Testata:
Journal of the Chemical Society. Dalton transactions
fascicolo: 4, , anno: 1997,
pagine: 469 - 478
SICI:
0300-9246(1997):4<469:CAO[(E>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
NUCLEAR-MAGNETIC-RESONANCE; GUANOSINE 5'-MONOPHOSPHATE; DRUG CARBOPLATIN; COMPLEXES; CISPLATIN; CIS-DIAMMINEDICHLOROPLATINUM(II); SPECTROSCOPY; PROTEINS; PRODUCTS; SULFUR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
40
Recensione:
Indirizzi per estratti:
Citazione:
Z.J. Guo et al., "CHELATE-RING-OPENED ADDUCTS OF [PT(EN)(ME-MAL-O,O')] (EN EQUALS ETHANE-1,2-DIAMINE, ME-MAL EQUALS 2-METHYLMALONATE) WITH METHIONINE DERIVATIVES - RELEVANCE TO THE BIOLOGICAL-ACTIVITY OF PLATINUM ANTICANCER AGENTS", Journal of the Chemical Society. Dalton transactions, (4), 1997, pp. 469-478

Abstract

The anticancer drug carboplatin [Pt(cbdca-O,O')(NH3)(2)] which contains the chelated dicarboxylate ligand cbdca, cyclobutane-1,1-dicarboxylate, may be activated in vivo by reaction with sulfur ligands. The reactions between the analogue [Pt(en)(Me-Mal-O,O')] 1 (en = ethane-1,2-diamine, Me-Mal = 2-methylmalonate) and the methionine derivatives N-acetyl-L-methionine (Ac-Met), glycyl-L-methionine (Gly-Met) and L-methionylglycine (Met-Gly) have been studied at pH 7 and 4, 310 K, using H-1and two-dimensional [H-1, N-15] heteronuclear single quantum coherence NMR spectroscopy and HPLC. The ring-opened species [Pt(en)(Me-Mal-O)(L-S)] (L = Ac-Met, Gly-Met or Met-Gly) containing monodentate malonate and S-bound monodentate methionine ligands were predominant in solution after 2 h. The second-order rate constant for the ring-opening reaction of 1 with Ac-Met at pH 6.56 was determined to be (1.48 +/- 0.03)x 10(-1) s(-1) M(-1), and was similar for reactions with Gly-Met. Methylmalonate alpha-CH deuteriation rates were determined to be free Me-Met > ring-opened complex much greater than 1. Molecular-mechanics modelling suggested that hydrogen bonding between the free carboxylate group of monodentate Me-Mal and the co-ordinated amine groups, and between the two ring-opened ligands may contribute to the stability of the mixed-ligand adducts. However, in the case of Met-Gly, the ring-opening rate [(5.26 +/- 0.10) x 10(-2) s(-1) M(-1)] was nearly three times slower than that for the reaction of 1 with Ac-Met. In contrast, the ring-closure rate of [Pt(en)(Me-Mal-O)(Met-Gly-S)] [k(1) = (1.37 +/- 0.03) x 10(-4) s(-1)] to give the S,N-chelated adduct was faster than that of [Pt(en)(Me-Mal-O)(Ac-Met-S)](-) 2 [(2.27 +/- 0.04) x 10(-5) s(-1)]. The S,N-chelated adducts [Pt(en)(Ac-MetH_(1)-S,N)] 3, [Pt(en)(Gly-MetH_(1)-S,N)](+) and [Pt(en)(Met-GlyH_(1)-S,N)](+) became the predominant products of the reactions after about 24 h. Ring-opened adducts ofchelated dicarboxylate platinum anticancer complexes with methionine derivatives could play a significant role in their mechanism of action.

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Documento generato il 19/09/20 alle ore 17:55:04