摘要
尽管铂类药物如顺铂、卡铂、奥沙利铂被广泛用于治疗人类肿瘤,但是铂药在正常和肿瘤细胞中的非选择性分布会引起严重的肠道反应、肾毒性、耳毒性、神经毒性等毒副作用,因而,其临床应用也受到了一定的限制.研究者对经典顺铂类抗肿瘤药物的开发已经付出了很多努力,但迄今为止仍然仅有少数几个得到世界范围内的广泛应用.过去的几十年中,大量非经典结构的铂抗肿瘤配合物被开发和研究,其通过与已上市经典结构的铂药不同的作用机制产生活性.本综述将讨论近年来非经典铂类抗肿瘤配合物的研究进展,为发现新的铂类抗癌药物提供一些启示.本文以非经典铂药的不同结构分为以下几类:具有以二甲胺和异丙胺等为配体的反式或单官能团配位的Pt(Ⅱ)配合物;以多胺、氨基酸或二羧酸、卤素离子为桥的多核铂配合物;以甲基吡啶为配体的具有空间位阻的铂配合物;含有主动靶向或被动靶向的Pt(Ⅳ)前药、氮杂环铂配合物和环金属铂配合物.
Although classical platinum-based drugs such as cisplatin,carboplatin and oxaliplatin are widely used in the therapy of human neoplasms,their clinical application is limited due to the non-selective distribution of platinum drugs in normal and tumor cells which could induce serious gastrointestinal reaction,nephrotoxicity,ototoxicity,neurotoxicity and other toxic side effects. Many efforts have been devoted to develop new platinum-based anticancer agents with classical structure,but only a few platinum drugs have been widely used in worldwide so far. Over the past a few years,a great number of non-classical structure platinum complexes have been extensively developed and investigated,because of their unique mechanism which are different from platinum drugs that have been marketed as classical structures. This paper discusses the research progress of non-classical platinum antitumor complexes in recent years,and provides some inspiration for the discovery of new platinum anticancer drugs. In this paper,according to different structures,non-classical platinum drugs are divided into the following categories： trans-or mono-functional coordination Pt（Ⅱ） complexes with dimetheyamine and is opropyamine as ligands; multi-nuclear platinum complexes bridged by polyamines,amino acids or carboxylic acids,and halogen ions; steric hindrance of complexes platinum complexes with picoline ligands; Pt（Ⅳ） prodrugs with active targeting or passive targeting; nitrogen heterocycles and ring metal platinum complexes.
作者
高传柱
蔡林祥
李军
张新忠
丛艳伟
杨波
普绍平
GAO Chuanzhu;CAI Linxiang;LI Jun;ZHANG Xinzhong;CONG Yanwei;YANG Bo;PU Shaoping(Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China;Kunming Guiyan Pharmaceutical Co. , Ltd. Kunming, 650106, China)
出处
《昆明理工大学学报（自然科学版）》
CAS
北大核心
2018年第3期70-82,共13页
Journal of Kunming University of Science and Technology(Natural Science)
基金
国家自然科学基金项目(21361014
21302074)
关键词
非经典构效关系
药物输送
抗肿瘤
多核铂
反式铂
Pt(Ⅳ)
non - classical structure - activity relationship
drug delivery
anticancer
muhiunclear
trans -platinum
Pt （Ⅳ）
