Influence of chemical stability on the activity of the antimetastasis ruthenium compound NAMI-A.
Influence of chemical stability on the activity of the antimetastasis ruthenium compound NAMI-A.
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DOI：
10.1016/s0959-8049(01)00389-6
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发表时间：
2002
影响因子：
8.4
通讯作者：
G. Sava;A. Bergamo;S. Zorzet;B. Gava;C. Casarsa;M. Cocchietto;A. Furlani;V. Scarcia;B. Serli;E. Iengo;E. Alessio;G. Mestroni
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文献类型：
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作者：
G. Sava;A. Bergamo;S. Zorzet;B. Gava;C. Casarsa;M. Cocchietto;A. Furlani;V. Scarcia;B. Serli;E. Iengo;E. Alessio;G. Mestroni
研究了抗肿瘤钌（III）化合物咪唑反式咪唑四氯二甲基亚砜钌（III）（NAMI-A）在水溶液中的体内外化学稳定性。通过使用在pH 3.0下用HCl酸化并老化0、4、8和24小时的NAMI-A溶液测试化合物中二甲基亚砜（DMSO）配体的损失，然后腹膜内（i. p.）注射到携带晚期MCa乳腺癌的CBA小鼠中。NAMI-A对肺转移的活性显示即使在DMSO配体从高达50%的分子损失后也没有变化。NAMI-A的还原没有改变在S+ G2 M期阻断的KB细胞的数量，与还原是否发生在细胞外或在用还原剂（抗坏血酸、谷胱甘肽或半胱氨酸）处理之前用化合物加载细胞之后无关。在体内，NAMI-A的完全还原与等量的抗坏血酸，谷胱甘肽或半胱氨酸给药前的晚期MCa乳腺癌小鼠比NAMI-A单独更积极。数据表明，NAMI-A，虽然经历了一系列的化学修饰，保持其抗转移活性在广泛的实验条件。
The influence of chemical stability on the antimetastatic ruthenium(III) compound imidazolium trans-imidazoletetrachlorodimethylsulphoxideruthenium(III) (NAMI-A) in aqueous solution was studied both in vitro and in vivo. The loss of dimethyl-sulphoxide (DMSO) ligand from the compound was tested by using a NAMI-A solution acidified with HCl at pH 3.0 and aged for 0, 4, 8 and 24 h prior to intraperitoneal (i.p.) injection into CBA mice bearing advanced MCa mammary carcinoma. The activity of NAMI-A on lung metastases showed no change even after the loss of DMSO ligand from up to 50% of the molecules. The reduction of NAMI-A did not modify the number of KB cells blocked in the S+G2M phases, independent of whether the reduction occurred outside the cells or after loading the cells with the compound prior to treatment with the reductants (ascorbic acid, glutathione or cysteine). In vivo, the complete reduction of NAMI-A with equivalent amounts of ascorbic acid, glutathione or cysteine prior to administration to mice bearing advanced MCa mammary carcinoma was more active than NAMI-A alone. The data show that NAMI-A, although undergoing a series of chemical modifications, maintains its antimetastatic activity in a broad range of experimental conditions.