摘要
拓扑异构酶(威尼斯平底渔船我)是核酶参与调整DNA拓扑结构在细胞周期的裂开,再次退火的两股DNA双螺旋结构。抑制这种酶导致DNA链断裂,最终导致细胞凋亡和细胞死亡;另外在实体肿瘤与健康组织提高水平。因此,威尼斯平底渔船我有巨大的潜力为目标的治疗肿瘤。虽然我第一威尼斯平底渔船抑制剂的重要的抗肿瘤活性,喜树碱(CPT),观察到在结肠癌、肺癌、卵巢癌、乳腺癌、肝脏、胰腺和胃癌症,CPT及其临床衍生品(topotecan和伊立替康)有几个限制。除了低水溶性和细胞抵抗部署,内酯开环导致细胞毒性活性和减少严重的副作用在生理条件下(pH值:7.4,37摄氏度)。虽然许多高效纳米药物输送系统为CPT开发及其衍生物来补偿这些化合物的障碍,到目前为止没有一个被批准。另一方面,有机non-CPT化合物已被搜索;indolocarbazoles indenoisoquinolines和dibenzonaphthyridines已经应用于临床的发展。尤其是indenoisoquinolines和dibenzonaphthyridines有利的特点相比,部署:化学稳定性;他们有能力克服细胞阻力,稳定enzyme-DNA乳沟复合物更持续。除了基于有机化合物的方法,最近一些金属配合物(如。、铂金、黄金、铜、钴、锌、钒、钌)也被报告为抑制剂的威尼斯平底渔船。本文将讨论策略针对威尼斯平底渔船的整个方面我在癌症化疗从过去的最近进展。
关键词: 癌症化疗
Current Drug Targets
Title:Strategies Targeting DNA Topoisomerase I in Cancer Chemotherapy: Camptothecins, Nanocarriers for Camptothecins, Organic Non-Camptothecin Compounds and Metal Complexes
Volume: 17 Issue: 16
Author(s): Kurtulus Gokduman
Affiliation:
关键词: 癌症化疗
摘要: Topoisomerase I (Topo I) is a nuclear enzyme engaged in adjustment of DNA topological structure during cell cycle by cleaving and reannealing one of the two strands of the DNA double helix. Inhibition of this enzyme results in DNA strand breaks, ultimately leads to apoptosis and cell death; additionally it is in raised level in solid tumors contrasted with healthy tissues. Consequently, Topo I has a great potential as a target for the treatment of tumors. Although significant anti-tumor activity of first Topo I inhibitor, camptothecin (CPT), was observed on colon, lung, ovarian, breast, liver, pancreas and stomach cancers, CPT and its clinical derivatives (topotecan and irinotecan) have several restrictions. In addition to their low water solubility and cell resistance to CPTs, lactone ring opening causes a reduction in cytotoxic activity and severe side effects in physiological conditions (pH: 7.4, 37°C). Although numerous efficient nano drug delivery systems were developed for CPT and its derivatives to compensate the handicaps of these compounds, none of them has been approved so far. On the other hand, organic non-CPT compounds have been searched; indolocarbazoles, indenoisoquinolines and dibenzonaphthyridines have been applied to clinical development. Especially, indenoisoquinolines and dibenzonaphthyridines have favorable characteristics compared to CPTs: They are chemically stable; they have the ability to overcome cell resistance; they stabilize enzyme-DNA cleavage complexes more persistently. In addition to the approaches based on organic compounds, recently some metal complexes (e.g., platinum, gold, copper, cobalt, zinc, vanadium, ruthenium) have also been reported as inhibitors of Topo I. This review will discuss the whole aspects of strategies targeting Topo I in cancer chemotherapy from past to the recent progresses.
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Kurtulus Gokduman , Strategies Targeting DNA Topoisomerase I in Cancer Chemotherapy: Camptothecins, Nanocarriers for Camptothecins, Organic Non-Camptothecin Compounds and Metal Complexes, Current Drug Targets 2016; 17 (16) . https://dx.doi.org/10.2174/1389450117666160502151707
DOI https://dx.doi.org/10.2174/1389450117666160502151707 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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