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新型混合配体配合物二正丁基 -(4 - 氯苯甲酰氧肟酸)锡(IV)氯化物的合成及其抗肿瘤活性

Synthesis and antitumor activity of a new mixed-ligand complex di-n-butyl-(4-chlorobenzohydroxamato)tin(IV) chloride.

作者信息

Li Yunlan, Li Yang, Niu Xiaoqiang, Jie Liujin, Shang Xianmei, Guo Jianping, Li Qingshan

机构信息

School of Pharmaceutical Science, Shanxi Medical University, 56 Xingjian South Road, Taiyuan, Shanxi Province 030001, PR China.

出版信息

J Inorg Biochem. 2008 Sep;102(9):1731-5. doi: 10.1016/j.jinorgbio.2008.05.002. Epub 2008 May 13.

Abstract

Reaction of di-n-butyltin(IV) dichloride with 4-chlorobenzohydroxamic acid at 1:1 ratio yielded a new mixed-ligand diorganotin(IV) complex, di-n-butyl-(4-chlorobenzohydroxamato)tin(IV) chloride(DBDCT). It was fully characterized by IR, (1)H, (13)C, (119)Sn NMR spectra and single crystal X-ray analysis. In DBDCT, the tin atom is five-coordinated in a trigonal bipyramidal geometry. DBDCT exhibited strong in vitro cytotoxic activity toward human immature granulocyte leukemia (HL-60), human salivary-gland carcinoma (SGC-7901), human henrietta carcinoma (Hela) and human urinary bladder (T24) cell lines which, in some cases, were equal to, or even higher than those of cis-dichlorodiammineplatinum(II) (cisplatin, DDP), the widely clinically used drug. The further in vivo antitumor tests of DBDCT towards the transplantation tumor models of sarcoma carcinoma (S(180)), hepatocellular carcinoma (H(22)) and Ehrlich's ascites carcinoma (EAC) on mice were carried out via injection intraperitoneally with cisplatin as positive contrast drug. The results showed that DBDCT displayed in vivo antitumor activity against the hepatocellular carcinoma H(22) and sarcoma carcinoma S(180) which were close to those of cisplatin, meanwhile, the survival-extending rates at middle dose and high dose on mice Ehrlich's ascites tumor EAC were higher than those of cisplatin, and there was a good dose-effect relationship.

摘要

二正丁基二氯化锡(IV)与4-氯苯甲羟肟酸按1:1比例反应生成了一种新型混合配体二有机锡(IV)配合物,二正丁基-(4-氯苯甲羟肟酸根)氯化锡(IV)(DBDCT)。通过红外光谱、(1)H、(13)C、(119)Sn核磁共振谱和单晶X射线分析对其进行了全面表征。在DBDCT中,锡原子以三角双锥几何构型五配位。DBDCT对人未成熟粒细胞白血病(HL-60)、人唾液腺癌(SGC-7901)、人子宫颈癌(Hela)和人膀胱癌(T24)细胞系表现出很强的体外细胞毒性活性,在某些情况下,其活性与临床上广泛使用的顺二氯二氨合铂(II)(顺铂,DDP)相当,甚至更高。以顺铂为阳性对照药物,通过腹腔注射对DBDCT对小鼠肉瘤癌(S(180))、肝癌(H(22))和艾氏腹水癌(EAC)移植瘤模型进行了进一步的体内抗肿瘤试验。结果表明,DBDCT对肝癌H(22)和肉瘤癌S(180)表现出体内抗肿瘤活性,与顺铂接近,同时,对小鼠艾氏腹水瘤EAC中剂量和高剂量的生存期延长率高于顺铂,且有良好的剂量效应关系。

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