摘要
铂(Pt)为基础的抗癌药物,例如顺铂,是联合化疗的关键组成部分。然而,毒性和抗药性阻碍他们的有效使用。它们与DNA结合并主要形成铂GG diadduct,随后导致细胞凋亡介导的细胞死亡。另一方面,铂药物–蛋白–代谢物之间的相互作用, 与PT和位于蛋白质侧链的硫位点以及重要的生物分子(如谷胱甘肽)的相互作用以及药物毒性和抗药性有关。因此,精心设计的协调配位体可以精细调整核心铂原子周围的电子环境,并允许所产生的铂化合物以不同的方式与核酸结合。这可能会使癌细胞的选择性细胞死亡,从而规避铂抵抗。本文综述了近年来发展的单功能铂配合物并讨论了其成为新一代抗癌药物的发展前景。
关键词: 顺铂,卡铂,奥沙利铂,铂类药物,单功能铂类药物。
Current Medicinal Chemistry
Title:Monofunctional Platinum (PtII) Compounds – Shifting the Paradigm in Designing New Pt-based Anticancer Agents
Volume: 23 Issue: 12
Author(s): Shu Xian Chong, Steve Chik Fun Au-Yeung, Kenneth Kin Wah To
Affiliation:
关键词: 顺铂,卡铂,奥沙利铂,铂类药物,单功能铂类药物。
摘要: Platinum (Pt)-based anticancer drugs, exemplified by cisplatin, are key components in combination chemotherapy. However, their effective use is hindered by toxicity and emergence of drug resistance. They bind to DNA and mainly form the Pt-GG diadduct, subsequently leading to apoptosis to mediate cell death. On the other hand, the Pt drug –proteins and –metabolites interactions, which involve the reaction between Pt and sulfur sites located in protein side chains and important bionucleophiles (e.g., glutathione), are responsible for the toxicity and drug resistance problem. Therefore, carefully designed coordinating ligands may provide the means of fine tuning the electronic environment around the core Pt atom and allow the resulting Pt compounds to bind with the DNA in a different manner. This may produce alternative cell death mechanisms in cancer cells, thereby circumventing Pt resistance. This article reviewed the recent development in monofunctional Pt complexes and their prospects in becoming a new generation of anticancer drugs.
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Shu Xian Chong, Steve Chik Fun Au-Yeung, Kenneth Kin Wah To , Monofunctional Platinum (PtII) Compounds – Shifting the Paradigm in Designing New Pt-based Anticancer Agents, Current Medicinal Chemistry 2016; 23 (12) . https://dx.doi.org/10.2174/0929867323666160311114509
DOI https://dx.doi.org/10.2174/0929867323666160311114509 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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