cis-[(trans-1,2-双(氨甲基)环丁烷)(3-羟基-1,1-环丁烷二羧酸根)合铂(Ⅱ)]的合成和抗癌活性  

Synthesis and Anticancer Activity of cis-[Pt(Ⅱ)(trans-1,2-bis(methylamino)cyclobutane)(3-hydroxyl-1,1-cyclobutanedicarboxylate)]

作　　者：高安丽[1] 邱洁 侯树谦[1] 姜婧[1] 楼丽广 刘伟平[1] 

机构地区：[1]昆明贵金属研究所,稀贵金属综合利用新技术国家重点实验室,昆明650106 [2]临沧市妇幼保健中心,临沧677000 [3]中国科学院上海药物研究所肿瘤药理研究室,上海201203

出　　处：《无机化学学报》2017年第5期837-842,共6页Chinese Journal of Inorganic Chemistry

基　　金：国家自然科学基金(NO.21661018);云南省科技计划项目(No.2014BC010,2016BC021)资助

摘　　要：通过对洛铂和卡铂的结构进行重组和优化,合成了一种新型洛铂衍生物cis-[(trans-1,2-双(氨甲基)环丁烷)(3-羟基-1,1-环丁烷二羧酸根)合铂(Ⅱ)],采用元素分析、红外光谱、质谱和核磁共振表征了其化学结构,并考察了此化合物的水溶性和稳定性。应用标准SRB法测试了目标化合物对人肺癌细胞株(NCI-H460、A549)、人乳腺癌细胞株(DU4475)、人白血病细胞株(Sup-B15)生长的抑制活性,评价了它对人肺癌细胞NCI-H460裸鼠移植瘤的治疗作用。结果表明:目标化合物水溶性好、稳定,对多种癌细胞的生长有明显的抑制活性,IC_(50)均小于10μmol·L^(-1)。更重要的是,其体内对人肺癌细胞NCI-H460裸鼠移植瘤的治疗效果明显,与洛铂相当。A new water-soluble and more water-stable analogue of lobaplatin, cis-[Pt（Ⅱ）（trans-l,2-bis（methylamino） cyclobutane）（3-hydroxyl-1,1-cyclobutanedicarboxylate）], was designed, with an attempt to improve the water-stability of lobaplatin while retaining its excellent anticancer profile, via the structural recombination and optimization of lobaplatin and carboplatin. The analogue was synthesized by the direct reaction between cis-[Pt（Ⅱ）（trans-l,2-bis （methylamino））I2] as an intermediate and the silver salt of 3-hydroxyl-1,1-eyclobutanedicarboxylic acid, and characterized by elemental analysis, ESI-MS, IR and 1H, 13C NMR. The anticancer activity was evaluated by both in vitro eyotoxicity against four human cancer cell lines and in vivo antitumor efficiency in human lung carcinoma NCI-H460 xenografts in nude mice. The biological tests revealed that the analogue produced significant inhibition of the tumor growth, resulting in an inhibitory rate of 54% at the dose of 60 mg.kg-1 and more importantly, it had in vivo anticancer activity comparable to that of lobaplatin.

关 键 词：铂类配合物 合成 表征 抗癌活性 

分 类 号：O614.826[理学—无机化学]