Synthesis, biological activity, and structure-activity relationships for potent cytotoxic rhodium(III) polypyridyl complexes

被引：59

作者：

Harlos, Melanie ^{[1
]}

Ott, Ingo ^{[2
]}

Gust, Ronald ^{[2
]}

Alborzinia, Hamed ^{[3
]}

Woelfl, Stefan ^{[3
]}

Kromm, Anna ^{[1
]}

Sheldrick, William S. ^{[1
]}

机构：

[1] Ruhr Univ Bochum, Lehrstuhl Analyt Chem, D-44780 Bochum, Germany

[2] Free Univ Berlin, Inst Pharm, D-14195 Berlin, Germany

[3] Univ Heidelberg, Inst Pharm & Mol Biotechnol, D-69120 Heidelberg, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 13期

关键词：

D O I：

10.1021/jm800173s

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The complexes mer-[RhCl3(DMSO-kS)(pp)] 1a-5a may be prepared by reaction of mer,cis-[RhCl3(DMSO-kS)(2)(DMSO-kO)] with the appropriate polypyridyl ligand (pp = bpy, phen, dpq, dppz, dppn) in CH3OH/H2O solution at 75 degrees C. The mer isomers of 1a-5a are stable in chloroform solution but those of 1a and 2a isomerize rapidly to a mixture of fac and mer isomers in DMSO. The complexes are potent in vitro cytotoxic agents and exhibit IC50 values that are strongly dependent on the size of the polypyridyl ligand IC50 values of, respectively, 4.0 (0.5) and 1.9 (0.5), 0.40 (0.06) and 0.19 (0.05), and 0.079 (0.012) and 0.069 (0.021) mu M are observed for 1a-3a against the human cell lines MCF-7 (breast cancer) and HT-29 (colon cancer). Cellular uptake studies showed a rapid and high accumulation of the polypyridyl compounds. Treatment of HT-29 and MCF-7 cells with 3a leads to significant decreases in cellular oxygen consumption and the rate of extracellular acidification.

引用

页码：3924 / 3933

页数：10

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