8-羟基喹啉类选择性铜离子螯合剂的合成及其体外抗肿瘤活性
Synthesis and in vitro Antitumor Activity of 8-Hydroxyquinoline-based Selective Copper Chelators
关颖祯 1何燕 2刘艳 3MEUNIER Bernard4
作者信息
- 1. 广东工业大学轻工化工学院,广东广州 510006
- 2. 广东工业大学生物医药学院,广东广州 510006
- 3. 广东工业大学轻工化工学院,广东广州 510006;广东省植物资源生物炼制重点实验室,广东广州 510006
- 4. 广东工业大学轻工化工学院,广东广州 510006;Lab.de Chimie de Coordination du CNRS,法国图卢兹31400
- 折叠
摘要
肿瘤与人体内铜离子稳态失衡密切相关.为了开发高效低毒的新型铜离子螯合剂类抗肿瘤化合物,以2-甲基-8-羟基喹啉为起始物,经过C-2位羟醛缩合、消除反应、迈克尔加成等反应合成5种8-羟基喹啉衍生物.通过紫外滴定法研究目标化合物的铜离子螯合能力和选择性;通过MTT法测定其对人黑色素瘤细胞(A375细胞和Colo829细胞)、人肺癌细胞(A549细胞)、人肝癌细胞(HepG2细胞)、人宫颈癌细胞(HeLa细胞)及人永生化角质形成细胞(HaCaT细胞)的细胞毒性.最终,得到安全性高于阳性对照品氟尿嘧啶(5-FU)的TDMQ51和TDMQ53这2个化合物,对铜和锌的络合常数相差达13个数量级,且对多种肿瘤细胞具有良好抑制活性,在提高抗肿瘤活性上具有改造潜力,可作为先导化合物进行深入研究.
Abstract
Tumor is closely related to the copper disorder in human body.In order to discover new copper ion chelating antitumor compounds,five 8-hydroxyquinoline derivatives were synthesized by C-2 aldol condensation,elimination and Michael reaction with 2-methyl-8-hydroxyquinoline as the starting material.The copper ion chelating ability and selectivity were studied by ultraviolet titration.And their cytotoxicity against human melanoma cells(A375 cells and Colo829 cells),human lung cancer cells(A549 cells),human liver cancer cells(HepG2 cells),human cervical cancer cells(HeLa cells)and human immortalized keratinocytes(HaCaT cells)was determined by MTT assay.Finally,two compounds TDMQ51 and TDMQ53 showed higher safety than the positive control fluorouracil(5-FU),while the complexation constants for copper and zinc differed by 13 orders of magnitude.These two compounds could be studied intensively as lead compounds owing to the good inhibitory activity to a wide variety of tumor cells.
关键词
8-羟基喹啉/体外抗肿瘤活性/铜离子螯合剂/选择性Key words
8-hydroxyquinoline/in vitro antitumor activity/copper ion chelating agent/selectivity引用本文复制引用
基金项目
国家自然科学基金(21977019)
广东省植物资源生物炼制重点实验室项目(2021B1212040011)
深圳市科技计划基金(2020N116)
出版年
2023
NETL
NSTL
维普
万方数据