Jain Chetan Kumar, Majumder Hemanta Kumar, Roychoudhury Susanta
Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata-700032, India.
Division of Research, Saroj Gupta Cancer Centre & Research Institute, M G Road, Thakurpukur, Kolkata-700 063, India.
Curr Genomics. 2017 Feb;18(1):75-92. doi: 10.2174/1389202917666160808125213.
DNA topoisomerases are important cellular enzymes found in almost all types of living cells (eukaryotic and prokaryotic). These enzymes are essential for various DNA metabolic processes e.g. replication, transcription, recombination, chromosomal decatenation etc. These enzymes are important molecular drug targets and inhibitors of these enzymes are widely used as effective anticancer and antibacterial drugs. However, topoisomerase inhibitors have some therapeutic limitations and they exert serious side effects during cancer chemotherapy. Thus, development of novel anticancer topoisomerase inhibitors is necessary for improving cancer chemotherapy. Nature serves as a repertoire of structurally and chemically diverse molecules and in the recent years many DNA topoisomerase inhibitors have been identified from natural sources. The present review discusses anticancer properties and therapeutic importance of eighteen recently identified natural topoisomerase inhibitors (from the year 2009 to 2015). Structural characteristics of these novel inhibitors provide backbones for designing and developing new anticancer drugs.
DNA拓扑异构酶是几乎在所有类型的活细胞(真核细胞和原核细胞)中都能找到的重要细胞酶。这些酶对于各种DNA代谢过程至关重要,例如复制、转录、重组、染色体解连环等。这些酶是重要的分子药物靶点,其抑制剂被广泛用作有效的抗癌和抗菌药物。然而,拓扑异构酶抑制剂存在一些治疗局限性,并且在癌症化疗期间会产生严重的副作用。因此,开发新型抗癌拓扑异构酶抑制剂对于改善癌症化疗是必要的。自然界是结构和化学性质多样的分子库,近年来已从天然来源鉴定出许多DNA拓扑异构酶抑制剂。本综述讨论了最近鉴定出的18种天然拓扑异构酶抑制剂(2009年至2015年)的抗癌特性和治疗重要性。这些新型抑制剂的结构特征为设计和开发新的抗癌药物提供了基础。