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DNA拓扑异构酶抑制剂
DNA Topoisomerase Inhibitors
DNA拓扑异构酶是一种广泛存在于真核细胞和原核细胞中的重要生物酶,对DNA转录、复制、染色体分离及基因表达等过程中的DNA拓扑结构起着重要的调控作用。研究发现,与正常细胞不同,DNA拓扑异构酶在肿瘤细胞中表现出不受其他因素影响的高水平表达,而许多抗肿瘤药物的作用机制也与DNA拓扑异构酶密切相关,因此它作为抗肿瘤药物的重要靶点引起了研究者的广泛关注。本文对DNA拓扑异构酶的结构、分类及生物功能进行了简要的归纳,总结了近年来DNA拓扑异构酶抑制剂的研究进展,并重点对金属配合物作为DNA拓扑异构酶抑制剂的研究现状进行了详细的介绍。
DNA topoisomerases (Topo) are ubiquitous enzymes in eukaryotic cell and prokaryotic cell. They are crucial for cellular genetic processes, such as replication, recombination, transcription, chromosome condensation, and the maintenance of genome stability by catalyzing the passage of individual DNA strands (topoisomerase Ⅰ) or double helices (topoisomerase Ⅱ) through one another. In accordance, topoisomerases are over expressed in cancer cell growth and thus are important cellular targets for anticancer drugs. The structures and biological functions of topoisomerases are discussed in this review. Moreover, some recent progresses of organic compounds and metal complexes as DNA topoisomerase inhibitors are discussed in detail.
Contents
1 Introduction
2 Structures and mechanisms of DNA topoisomerases
2.1 Structures of DNA topoisomerases
2.2 Mechanisms of DNA topoisomerases
3 Biological functions of DNA topoisomerases
3.1 Regulation of topological states of DNA
3.2 Role of DNA topoisomerases in recombination and repair
4 DNA topoisomerases inhibitors
4.1 Mechanisms of DNA topoisomerase inhibition
4.2 Organic compounds as DNA topoisomerase inhibitors
4.3 Metal complexes as DNA topoisomerase inhibitors
5 Perpective
DNA拓扑异构酶
DNA topoisomerase
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