NEW ANTITUMOR PLATINUM COMPOUNDS LINKED TO AMINO PHOSPHONIC-ACIDS WHICH LOSE THE PHOSPHONATE AND TERTIARY AMINE LIGAND UPON BINDING TO NUCLEIC-ACIDS

被引:50
作者
BLOEMINK, MJ
DORENBOS, JP
HEETEBRIJ, RJ
KEPPLER, BK
REEDIJK, J
ZAHN, H
机构
[1] LEIDEN UNIV,LEIDEN INST CHEM,GORLAEUS LABS,POB 9502,2300 RA LEIDEN,NETHERLANDS
[2] UNIV HEIDELBERG,INST ANORGAN CHEM,D-69120 HEIDELBERG,GERMANY
关键词
D O I
10.1021/ic00084a026
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
The interaction of the antitumor active platinum phosphonato complexes [cis-Pt(NH3)2(ntmp)] and [Pt(R,S-dach)(ntmp)] (ntmp = nitrilotris(methylenephosphonic acid), dach = diaminocyclohexane) with (oligo)nucleotides has been investigated using H-1 NMR and P-31 NMR spectroscopy. For both complexes the formation of GN7,GN7 chelates is observed, together with the release of ntmp. First, the platinum-phosphonate bond is broken, probably by direct attack of the first G-base. The coordination of the second base is accompanied by breakage of the bond between the Pt(II) ion and the tertiary amine ligand, a very unusual observation, as N-donor ligands generally act as nonleaving groups in platinum antitumor chemistry. For this type of platinum antitumor complexes of which the strucural formula seems to violate the classical structure-activity relationships, both pH and nonleaving amine group do influence the rate of the reaction with (oligo)nucleotides significantly.
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收藏
页码:1127 / 1132
页数:6
相关论文
共 49 条
  • [1] NMR-SPECTRA OF IMINOBIS(METHYLENEPHOSPHONIC ACID), HN(CH2PO3H2)2, AND RELATED LIGANDS AND OF THEIR COMPLEXES WITH PLATINUM(II)
    APPLETON, TG
    HALL, JR
    MCMAHON, IJ
    [J]. INORGANIC CHEMISTRY, 1986, 25 (06) : 726 - 734
  • [2] COORDINATION OF AQUATED CIS-PLATINUM(II) DIAMINES TO PURINE NUCLEOSIDES - KINETICS OF COMPLEX-FORMATION
    ARPALAHTI, J
    LIPPERT, B
    [J]. INORGANIC CHEMISTRY, 1990, 29 (01) : 104 - 110
  • [3] PLATINUM COMPOUNDS WITH ESTROGEN-RECEPTOR AFFINITY
    BEDNARSKI, PJ
    GUST, R
    SPRUSS, T
    KNEBEL, N
    OTTO, A
    EARBEL, M
    KOOP, R
    HOLLER, E
    VONANGERER, E
    SCHONENBERGER, H
    [J]. CANCER TREATMENT REVIEWS, 1990, 17 (2-3) : 221 - 231
  • [4] KINETIC PREFERENCE OF 5'GMP OVER 3'GMP IN REACTIONS WITH PLATINUM AMINE COMPOUNDS AS STUDIED BY COMPETITION REACTIONS
    BLOEMINK, MJ
    LEMPERS, ELM
    REEDIJK, J
    [J]. INORGANICA CHIMICA ACTA, 1990, 176 (02) : 317 - 320
  • [5] CURT GA, 1983, CANCER RES, V43, P4470
  • [6] CISPLATIN NEPHROTOXICITY - A REVIEW
    DAUGAARD, G
    ABILDGAARD, U
    [J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY, 1989, 25 (01) : 1 - 9
  • [7] CONFORMATIONAL-ANALYSIS OF THE ADDUCT CIS-[PT(NH3)2(D(GPG))]+ IN AQUEOUS-SOLUTION - A HIGH-FIELD (500-300 MHZ) NUCLEAR MAGNETIC-RESONANCE INVESTIGATION
    DENHARTOG, JHJ
    ALTONA, C
    CHOTTARD, JC
    GIRAULT, JP
    LALLEMAND, JY
    DELEEUW, FAAM
    MARCELIS, ATM
    REEDIJK, J
    [J]. NUCLEIC ACIDS RESEARCH, 1982, 10 (15) : 4715 - 4730
  • [8] REACTION-PRODUCTS OF CIS-DIAMMINEPLATINUM(II) COMPOUNDS WITH 5'-GUANOSINE MONOPHOSPHATE CHARACTERIZED BY HIGH-FREQUENCY PROTON NMR
    DIJT, FJ
    CANTERS, GW
    DENHARTOG, JHJ
    MARCELIS, ATM
    REEDIJK, J
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1984, 106 (12) : 3644 - 3647
  • [9] KINETIC-STUDIES ON THE DIAQUA FORM OF CISPLATIN AND VARIOUS NUCLEOBASES
    EAPEN, S
    GREEN, M
    ISMAIL, IM
    [J]. JOURNAL OF INORGANIC BIOCHEMISTRY, 1985, 24 (03) : 233 - 237
  • [10] KINETIC AND THERMODYNAMIC SELECTIVITY IN THE REACTIONS OF THE DIAQUA FORM OF CISPLATIN WITH 3'-GUANOSINEMONOPHOSPHORIC AND 5'-GUANOSINEMONOPHOSPHORIC ACID
    EVANS, DJ
    FORD, NR
    GREEN, M
    [J]. INORGANICA CHIMICA ACTA-BIOINORGANIC CHEMISTRY, 1986, 125 (03): : L39 - L40