The influence of calcium ions on the DNA binding behaviour of a new platinum(II) compound linked to an amino phosphonic acid

被引：16

作者：

Einhauser, TJ ^{[1
]}

Galanski, M ^{[1
]}

Vogel, E ^{[1
]}

Keppler, BK ^{[1
]}

机构：

[1] UNIV HEIDELBERG,INST ANORGAN CHEM,D-69120 HEIDELBERG,GERMANY

来源：

INORGANICA CHIMICA ACTA | 1997年 / 257卷 / 02期

关键词：

osteotropic platinum phosphonic acid complexes; calcium ions; DNA binding behaviour; antitumour activity;

D O I：

10.1016/S0020-1693(96)05477-1

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

The binding behaviour towards DNA of the new osteatropic platinum phosphonato complex [cis-Pt(NH3)(2)(sPMAA)], 1, (BPMAA = bis( phosphonomethyl) aminoacetic acid),has been investigated. The slow hydrolysis kinetics of 1 and the low antitumour activity in vitro is in contrast to the antitumour activity found in vivo. This strongly suggests an activation mechanism facilitating the formation of an adduct with DNA. The fact that a dramatic increase in the binding rate can be observed in the presence of Ca2+ ions and the fact that there is an increased calcium concentration in the region of bone tumours may explain the antitumour activity of 1 against bone tumours.

引用

页码：265 / 268

页数：4

共 17 条

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

BLOEMINK, MJ ;

DORENBOS, JP ;

HEETEBRIJ, RJ ;

KEPPLER, BK ;

REEDIJK, J ;

ZAHN, H .

INORGANIC CHEMISTRY, 1994, 33 (06) :1127-1132

[2]

BLOEMINK MJ, UNPUB INORG CHIM ACT

[3]

EINHAUSER TJ, 1996, THESIS HEIDELBERG

[4]

GALANSKI M, 1995, ANGEW CHEM, V107, P1220

[5] NEW PLATINUM ANTITUMOR COMPLEXES [J].

KELLAND, LR .

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 1993, 15 (03) :191-219

[6]

KELLAND LR, 1992, PLATIN MET REV, V36, P178

[7] ANTICANCER-AGENT-LINKED PHOSPHONATES WITH ANTIOSTEOLYTIC AND ANTINEOPLASTIC PROPERTIES - A PROMISING PERSPECTIVE IN THE TREATMENT OF BONE-RELATED MALIGNANCIES [J].

KLENNER, T ;

WINGEN, F ;

KEPPLER, BK ;

KREMPIEN, B ;

SCHMAHL, D .

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 1990, 116 (04) :341-350

[8] THERAPEUTIC EFFICACY OF 2 DIFFERENT CYTOSTATIC-LINKED PHOSPHONATES IN COMBINATION WITH RAZOXANE IN THE TRANSPLANTABLE OSTEOSARCOMA OF THE RAT [J].

KLENNER, T ;

WINGEN, F ;

KEPPLER, B ;

VALENZUELAPAZ, P ;

AMELUNG, F ;

SCHMAHL, D .

CLINICAL & EXPERIMENTAL METASTASIS, 1990, 8 (04) :345-359

[9]

Klenner T., 1993, METAL COMPLEXES CANC, P85

[10] THE HYDROLYSIS PRODUCTS OF CIS-DICHLORODIAMMINEPLATINUM(II) .3. HYDROLYSIS KINETICS AT PHYSIOLOGICAL PH [J].

MILLER, SE ;

HOUSE, DA .

INORGANICA CHIMICA ACTA, 1990, 173 (01) :53-60

← 1 2 →