Bonire J J, Fricker S P
Department of Chemistry, Ahmadu Bello University, Zaria, Nigeria.
J Inorg Biochem. 2001 Jan 15;83(2-3):217-21. doi: 10.1016/s0162-0134(00)00192-6.
Platinum compounds containing the ligand 1,2-diaminocyclohexane (DACH) such as tetraplatin [PtCl4(DACH)] have been found to be active in cisplatin-resistant tumour models. In an attempt to develop novel metal-based drugs with a different therapeutic profile to cisplatin, we have synthesised a series of tin compounds containing the DACH ligand, including the Sn analogue of tetraplatin [SnCl4(DACH)], and the di- and monoorganotin complexes [Ph2Sn(OAc)2(DACH)], [Bu2Sn(OAc)2(DACH)], [PhSnCl3(DACH)], [BuSn(OAc)3(DACH)], [BuSnCl3(DACH)], and [PhSn(OCOCF3)3(DACH)]. Mossbauer and IR spectroscopy indicates that the Sn(DACH) complexes are hexacoordinated with a molecular structure similar to that of tetraplatin. These compounds were tested for potential antitumour activity against a panel of human tumour cell lines, (SW620, SW1116 colon carcinoma, ZR-75-1 breast carcinoma, HT1376 bladder carcinoma, SKOV-3, PA-1 ovarian carcinoma). [Ph2Sn(penicillinate)], [Ph2Sn(OCOCH2NCOCH2NH2)], [Ph2Sn(OAc)2] were included for comparison. The results show that whereas [SnCl4(DACH)] and the monoorganotin complexes had limited or no activity, the diorganotin DACH complexes were cytotoxic with an associated increase in potency on going from diphenyl to dibutyltin, with mean IC50 values of 7.26+/-4.09 micromol ml(-1) for [Ph2Sn(OAc)2(DACH)] and 2.58+/-0.83 micromol ml(-1) for [Bu2Sn(OAc)2(DACH)] across the cell line panel. Comparison with [Ph2Sn(OAc)2] (IC50 0.69-0.43 micromol ml(-1)) indicated that addition of the DACH ligand resulted in a decrease in cytotoxicity but increased differential toxicity across the cell line panel. These results indicate that the diorganotin DACH complexes merit further investigation as potential metal-based antitumour drugs.
含1,2 - 二氨基环己烷（DACH）配体的铂化合物，如四铂[PtCl4(DACH)]，已被发现在顺铂耐药肿瘤模型中具有活性。为了开发具有与顺铂不同治疗特性的新型金属基药物，我们合成了一系列含DACH配体的锡化合物，包括四铂的锡类似物[SnCl4(DACH)]，以及二有机锡和单有机锡配合物[Ph2Sn(OAc)2(DACH)]、[Bu2Sn(OAc)2(DACH)]、[PhSnCl3(DACH)]、[BuSn(OAc)3(DACH)]、[BuSnCl3(DACH)]和[PhSn(OCOCF3)3(DACH)]。穆斯堡尔谱和红外光谱表明，Sn(DACH)配合物是六配位的，其分子结构与四铂相似。对这些化合物针对一组人类肿瘤细胞系（SW620、SW1116结肠癌、ZR - 75 - 1乳腺癌、HT1376膀胱癌、SKOV - 3、PA - 1卵巢癌）进行了潜在抗肿瘤活性测试。为作比较，还纳入了[Ph2Sn(青霉素盐)]、[Ph2Sn(OCOCH2NCOCH2NH2)]、[Ph2Sn(OAc)2]。结果表明，虽然[SnCl4(DACH)]和单有机锡配合物活性有限或无活性，但二有机锡DACH配合物具有细胞毒性，且从二苯基锡到二丁基锡时活性相关增加，在整个细胞系组中，[Ph2Sn(OAc)2(DACH)]的平均IC50值为7.26±4.09 μmol ml(-1)，[Bu2Sn(OAc)2(DACH)]的平均IC50值为2.58±0.83 μmol ml(-1)。与[Ph2Sn(OAc)2]（IC50为0.69 - 0.43 μmol ml(-1)）比较表明，添加DACH配体导致细胞毒性降低，但增加了整个细胞系组的差异毒性。这些结果表明，二有机锡DACH配合物作为潜在的金属基抗肿瘤药物值得进一步研究。
