| 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 | 单位 | E-mail | | 高安丽 | 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 | | | 邱洁 | 临沧市妇幼保健中心, 临沧 677000 | | | 侯树谦 | 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 | | | 姜婧 | 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 | dianaair@126.com | | 楼丽广 | 中国科学院上海药物研究所肿瘤药理研究室, 上海 201203 | | | 刘伟平 | 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 | liuweiping1963@126.com |
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| 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，IC50均小于10 μmol·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。 |
| 关键词: 铂类配合物 合成 表征 抗癌活性 |
| 基金项目: 国家自然科学基金（NO.21661018）和云南省科技计划项目（No.2014BC010，2016BC021）资助。 |
| Abstract: A new water-soluble and more water-stable analogue of lobaplatin, cis-[Pt(Ⅱ)(trans-1,2-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-1,2-bis(methylamino))I2] as an intermediate and the silver salt of 3-hydroxyl-1,1-cyclobutanedicarboxylic acid, and characterized by elemental analysis, ESI-MS, IR and 1H, 13C NMR. The anticancer activity was evaluated by both in vitro cyotoxicity 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. |
| Keywords: platinum complexes synthesis characterization anticancer activity |
| 投稿时间：2016-12-01 修订日期：2017-03-14 |
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| 高安丽,邱洁,侯树谦,姜婧,楼丽广,刘伟平.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[J].无机化学学报,2017,33(5):837-842. |
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