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首页> 外文期刊>Journal of applied toxicology >Cell proliferation inhibition and antitumor activity of novel alkyl series of diorganotin(IV) compounds.
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Cell proliferation inhibition and antitumor activity of novel alkyl series of diorganotin(IV) compounds.

机译：二有机锡（IV）新型烷基系列的细胞增殖抑制作用和抗肿瘤活性。

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Diorganotin(IV) compounds, R2SnCl2 are often tetrahedral, and structurally resemble the active platinum compounds, i.e. cisplatin, and consequently a large number of such complexes have been tested for antitumor activity. A structural correlation with biological activity for diorganotin(IV) complexes has shown that active species are associated with complexes having Sn-N bonds longer than 2.39 A which in turn determines the formation of a tin-DNA complex. In view of these, a series of diorganotin(IV) dichloride complexes of N-(2-pyridylmethylene)arylamine (nitrogen-chelating ligands) has been synthesized and characterized on the basis of IR, NMR and 119Sn-Mossbauer studies. In the present study, an attempt was made to determine the comparative antiproliferative and antitumor effect of diorganotin(IV) complexes with different alkyl groups [Me2SnCl2.L1 (OTC-1), Et2SnCl2.L2 (OTC-2) and (n)Bu2SnCl2.L2 (OTC-3)]. The present study in human lymphocytes demonstrated that these diorganotin(IV) complexes could block the cell cycle progression and induce sister chromatid exchanges (SCEs) significantly, however, with respect to the induction of chromosome aberrations (CAs) it was very mild. Both the levels of p53 and p16 proteins were raised after diorganotin(IV) treatment and such induction was maximum in the OTC-3 treated samples. The antitumor activity was determined in accordance with the US National Cancer Institute (NCI) standard protocol for primary screening in Dalton's lymphoma that was maintained by serial intraperitoneal transplantation. The T/C (treated/control) value was increased (186% with OTC-3) when diorganotin(IV) was given after transplantation. The data suggest that the OTC-3 has better antiproliferative and antitumor activity and endogenous glutathione level has no influence on the effect of OTC-3.
机译：二有机锡（IV）化合物R 2 SnCl 2通常是四面体的，并且在结构上类似于活性铂化合物即顺铂，因此已经测试了大量此类复合物的抗肿瘤活性。二有机锡（IV）配合物与生物活性的结构相关性表明，活性物质与Sn-N键长于2.39 A的配合物相关，这反过来又决定了锡-DNA配合物的形成。鉴于这些，已经合成了一系列N-（2-吡啶基亚甲基）芳基胺（氮螯合配体）的二氯化二有机锡（IV）配合物，并基于IR，NMR和119Sn-Mossbauer进行了表征。在本研究中，试图确定具有不同烷基[Me2SnCl2.L1（OTC-1），Et2SnCl2.L2（OTC-2）和（n）Bu2SnCl2的二有机锡（IV）配合物的比较抗增殖和抗肿瘤作用。 .L2（OTC-3）]。目前在人类淋巴细胞中的研究表明，这些二有机锡（IV）复合物可以阻断细胞周期进程并显着诱导姐妹染色单体交换（SCE），但是，在诱导染色体畸变（CA）方面，它是非常温和的。在二有机锡（IV）处理后，p53和p16蛋白的水平均升高，并且这种诱导在OTC-3处理的样品中最大。抗癌活性是根据美国国家癌症研究所（NCI）标准方案确定的，用于通过连续腹膜内移植维持的道尔顿淋巴瘤的初步筛查。移植后给予双有机锡（IV）时，T / C（治疗/对照）值增加（OTC-3为186％）。数据表明，OTC-3具有更好的抗增殖和抗肿瘤活性，内源性谷胱甘肽水平对OTC-3的作用没有影响。

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