水溶性铜卟啉配合物的合成、与DNA的相互作用及抗肿瘤活性

合成了3种水溶性铜卟啉配合物,分别为水溶性含溴铜卟啉(CuP-1)及其溴取代衍生物(CuP-2、CuP-3),并采用核磁氢谱、元素分析、质谱等手段进行了结构表征。利用紫外光谱法、EB-DNA荧光淬灭法、粘度法以及圆二色谱法等光谱法研究了CuP-1、CuP-2和CuP-3与小牛胸腺DNA(CT-DNA)的相互作用。采用噻唑兰(MTT)法,以体外培养的宫颈癌细胞(Hela)和乳腺癌细胞(MDA)为测试细胞株对CuP-1~CuP-3的抗肿瘤活性进行检测。人成纤维细胞(L929)作为正常细胞系。光谱法实验结果表明,CuP-1以插入的方式与CT-DNA相互作用,而CuP-2和CuP-3与CT-DNA以沟面结合的方式相互作用,且CuP-1与CT-DNA的结合能力优于CuP-2和CuP-3。体外抗癌活性实验结果表明,CuP-1~CuP-3对Hela和MDA均有体外抑制细胞增殖作用,呈时间、剂量依赖关系,并且CuP-1的体外抗肿瘤活性明显优于CuP-2、CuP-3。

Syntheses, DNA-binding and Antitumor Activities of Water Soluble Copper Porphyrins Complexes

Three water-soluble copper porphyrin complexes (water-soluble bromine-containing copper porphyrin CuP-1 and its bromine substituted derivatives CuP-2 and CuP-3) have been synthesized and characterized by ¹H NMR, elementary analysis and MS spectra. The interaction of CuP-1, CuP-2 and CuP-3 with CT-DNA have been investigated by UV spectrum, EB-DNA fluorescence quenching, viscosity method and circular dichroism spectrum. Moreover, the antitumor activities of CuP-1~CuP-3 against Hela (cervical cancer) cell lines and MDA (breast carcinoma) cell lines have been studied by MTT assay. L929 (human fibroblast) cell line was used as a normal cell lines. Various spectroscopic approaches indicates that CuP-1 could effectively bind with CT-DNA through intercalation mode, while CuP-2 and CuP-3 may interact with CT-DNA by outside groove binding mode. And the binding affinity of CuP-1 with CT-DNA is better than its derivatives CuP-2 and CuP-3. In vitro antitumor activity experiments showed that CuP-1~CuP-3 can inhibit the growth of Hela and MDA cell lines, and the inhibition shows concentration and time dependent. In addition, antitumor activity in vitro of CuP-1 is much better than CuP-2 and CuP-3.