Influence of the anionic ligands on the anticancer activity of Ru(II)-dmso complexes: Kinetics of aquation and in vitro cytotoxicity of new dicarboxylate compounds in comparison with their chloride precursors

被引：20

作者：

Bratsos, Ioannis ^{[1
]}

Bergamo, Alberta ^{[3
]}

Sava, Gianni ^{[3
]}

Gianferrara, Teresa ^{[2
]}

Zangrando, Ennio ^{[1
]}

Alessio, Enzo ^{[1
]}

机构：

[1] Univ Trieste, Dipartimento Sci Chim, I-34127 Trieste, Italy

[2] Univ Trieste, Dipartimento Sci Farmaceut, I-34127 Trieste, Italy

[3] Callerio Fdn Onlus, I-34127 Trieste, Italy

来源：

JOURNAL OF INORGANIC BIOCHEMISTRY | 2008年 / 102卷 / 04期

关键词：

dicarboxylates; kinetics; ruthenium; dimethylsulfoxide; anticancer;

D O I：

10.1016/j.jinorgbio.2007.10.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We performed extensive studies on the kinetics of hydrolysis of a series of Ru(II)-dmso complexes containing dicarboxylate ligands, such as oxalate, malonate, succinate and 1,1-cyclobutane dicarboxylate (cbdc), derived from anticancer-active Ru(II)-dmso-Cl precursors. The in vitro antitumor activity of those compounds in comparison with their chloride precursors was evaluated against two tumor cell lines, the human KB oral carcinoma and the murine B16-F10 melanoma. The aim of this study was to assess how the nature of the anionic ligands (i.e. dicarboxylates vs. chlorides) affects the chemical behavior and the in vitro antitumor activity of Ru(II)-dmso complexes. Among the tested compounds only one complex, the dimer [fac-Ru(dmso-S)(3)(H2O)(mu-cbdc)](2) (5), exhibited moderate activity against both cell lines. Interestingly, this compound is the most kinetically stable in aqueous solution among those investigated. Despite the moderate in vitro activity, in an in vivo test, complex 5 exhibited no activity against both the primary tumor growth and the formation of spontaneous metastases on the MCa mammary carcinoma model. (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：606 / 617

页数：12

共 31 条

[1] Ruthenium antimetastatic agents [J].

Alessio, E ;

Mestroni, G ;

Bergamo, A ;

Sava, G .

CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2004, 4 (15) :1525-1535

[2] CIS-DIHALOTETRAKIS(DIMETHYL SULFOXIDE)RUTHENIUM(II) AND TRANS-DIHALOTETRAKIS(DIMETHYL SULFOXIDE)RUTHENIUM(II) COMPLEXES (RUX2(DMSO)4, X = CL, BR) - SYNTHESIS, STRUCTURE, AND ANTITUMOR-ACTIVITY [J].

ALESSIO, E ;

MESTRONI, G ;

NARDIN, G ;

ATTIA, WM ;

CALLIGARIS, M ;

SAVA, G ;

ZORZET, S .

INORGANIC CHEMISTRY, 1988, 27 (23) :4099-4106

[3]

ALLEY MC, 1988, CANCER RES, V48, P589

[4] Development of organometallic ruthenium-arene anticancer drugs that resist hydrolysis [J].

Ang, Wee Han ;

Daldini, Elisa ;

Scolaro, Claudine ;

Scopelliti, Rosario ;

Juillerat-Jeannerat, Lucienne ;

Dyson, Paul J. .

INORGANIC CHEMISTRY, 2006, 45 (22) :9006-9013

[5]

[Anonymous], 1999, J. Appl. Crystallogr, DOI [DOI 10.1107/S0021889899006020, 10.1107/S0021889899006020]

[6] The hydrolysis of the anti-cancer ruthenium complex NAMI-A affects its DNA binding and antimetastatic activity: an NMR evaluation [J].

Bacac, M ;

Hotze, ACG ;

van der Schilden, K ;

Haasnoot, JG ;

Pacor, S ;

Alessio, E ;

Sava, G ;

Reedijk, J .

JOURNAL OF INORGANIC BIOCHEMISTRY, 2004, 98 (02) :402-412

[7]

Bergamo A, 2002, INT J ONCOL, V21, P1331

[8] The unprecedented bridging coordination mode of 1,1-cyclobutane dicarboxylate (μ-cbdc-O,O′) stabilized by intramolecular hydrogen bonds in ruthenium(II) complexes [J].

Bratsos, I ;

Zangrando, E ;

Serli, B ;

Katsaros, N ;

Alessio, E .

DALTON TRANSACTIONS, 2005, (24) :3881-3885

[9] Replacement of chlorides with dicarboxylate ligands in anticancer active Ru(II)-DMSO compounds: A new strategy that might lead to improved activity [J].

Bratsos, Ioannis ;

Serli, Barbara ;

Zangrando, Ennio ;

Katsaros, Nikos ;

Alessio, Enzo .

INORGANIC CHEMISTRY, 2007, 46 (03) :975-992

[10] Non-platinum chemotherapeutic metallopharmaceuticals [J].

Clarke, MJ ;

Zhu, FC ;

Frasca, DR .

CHEMICAL REVIEWS, 1999, 99 (09) :2511-2533

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