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诱导凋亡的二茂钒化合物抗人睾丸癌研究

Apoptosis-inducing vanadocene compounds against human testicular cancer.

作者信息

Ghosh P, D'Cruz O J, Narla R K, Uckun F M

机构信息

Drug Discovery Program, Parker Hughes Institute, St. Paul, Minnesota 55113, USA.

出版信息

Clin Cancer Res. 2000 Apr;6(4):1536-45.

Abstract

We systematically assessed the cytotoxic effects of five metallocene dichlorides containing vanadium (vanadocene dichloride), titanium (titanocene dichloride), zirconium (zircodocene dichloride), molybdenum (molybdocene dichloride), and hafnium (hafnocene dichloride) as the central metal atom and 19 other vanadocene complexes. These compounds were tested against the human testicular cancer cell lines Tera-2 and Ntera-2 using both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and apoptosis assays. Notably, only the vanadium(IV)-containing metallocenes exhibited significant cytotoxicity against Tera-2 and Ntera-2 cells and induced apoptosis within 24 h. Vanadocenes with dithiocyanate [VCp2(SCN)2 x 0.5 H2O] and diselenocyanate [VCp2(NCSe)2] as ancillary ligands were identified as the most potent cytotoxic compounds. Vanadocenes, especially the lead compound VCp2(NCSe)2, may be useful in the treatment of testicular cancer.

摘要

我们系统地评估了五种以钒(二氯茂钒)、钛(二氯茂钛)、锆(二氯茂锆)、钼(二氯茂钼)和铪(二氯茂铪)作为中心金属原子的二氯化金属茂以及其他19种钒茂配合物的细胞毒性作用。使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐试验和凋亡试验,将这些化合物针对人睾丸癌细胞系Tera-2和Ntera-2进行了测试。值得注意的是,只有含钒(IV)的金属茂对Tera-2和Ntera-2细胞表现出显著的细胞毒性,并在24小时内诱导凋亡。以硫氰酸盐[VCp2(SCN)2·0.5H2O]和二硒氰酸盐[VCp2(NCSe)2]作为辅助配体的钒茂被确定为最有效的细胞毒性化合物。钒茂,尤其是先导化合物VCp2(NCSe)2,可能对睾丸癌的治疗有用。

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