Development of cobalt(3,4-diarylsalen) complexes as tumor therapeutics
Development of cobalt(3,4-diarylsalen) complexes as tumor therapeutics
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DOI：
10.1021/jm040763n
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发表时间：
2004-11-18
影响因子：
7.3
通讯作者：
Sommer, K
中科院分区：
文献类型：
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作者：
Gust, R;Ott, I;Sommer, K
[1,6-二（2-羟基苯基）-3,4-二芳基-2,5-二氮杂杂基-1,5-二烯基钴（II）配合物（钴（3,4-二芳基salen））))在3,4位芳基环上具有2-、3-或4-OCH3/OH取代基，并在MCF-7、MDA-MB 231和LNCaP/FGC细胞系上进行了体外抗肿瘤活性测试。]细胞毒性与二烯配体的构型和3,4-立环取代基的种类有关。d,1-7 (2-OCH3), d,1-8 （3-OCH3）和d，1-9 （4-OCH3）对顺铂具有同等的效力，而各自的羟基取代配合物(d,1-10 （2-OH), d,1-11 （3-OH）和d，1-12 (2-OH)）以及所有中位结构化合物（m-7至m-12）对细胞生长没有影响。有趣的是，在MCF-7细胞中，m-7 （2-OCH3）、m-8 （3-OCH3）和m-9 （4-OCH3）具有高的催化效力和快速和高的积累（与细胞培养基（5 muM）相比，15至25倍）。因此，基于钴催化的DNA氧化损伤的作用模式不太可能。
[1,6-Bis(2-hydroxyphenyl)-3,4-diaryl-2,5-diazahexa-1,5-dienelcobalt(II) complexes (cobalt(3,4-diarylsalen)) with 2-, 3-, or 4-OCH3/OH substituents in the 3,4-standing aryl rings were synthesized and tested for antitumor activity in vitro on the MCF-7, MDA-MB 231, and LNCaP/FGC cell lines. The cytotoxicity depended on both the configuration of the diene ligand and the kind of substituents in the 3,4-standing aromatic rings. d,1-7 (2-OCH3), d,1-8 (3-OCH3) and d,1-9 (4-OCH3) were equipotent to cisplatin, while the respective hydroxy-substituted complexes (d,1-10 (2-OH), d,1-11 (3-OH), and d,1-12 (2-OH)) as well as all of the meso-configured compounds (m-7 to m-12) did not influence the cell growth. Interestingly, a high catalytic potency and a rapid and high accumulation in MCF-7 cells (15- to 25-fold compared to the cell culture medium (5 muM)) were demonstrated for m-7 (2-OCH3), m-8 (3-OCH3) and m-9 (4-OCH3). Therefore, a mode of action based on a cobalt-catalyzed oxidative damage of the DNA is not very likely.