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顺铂:第一种金属类抗癌药物。

Cisplatin: The first metal based anticancer drug.

机构信息

Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.

出版信息

Bioorg Chem. 2019 Jul;88:102925. doi: 10.1016/j.bioorg.2019.102925. Epub 2019 Apr 11.

Abstract

Cisplatin or (SP-4-2)-diamminedichloridoplatinum(II) is one of the most potential and widely used drugs for the treatment of various solid cancers such as testicular, ovarian, head and neck, bladder, lung, cervical cancer, melanoma, lymphomas and several others. Cisplatin exerts anticancer activity via multiple mechanisms but its most acceptable mechanism involves generation of DNA lesions by interacting with purine bases on DNA followed by activation of several signal transduction pathways which finally lead to apoptosis. However, side effects and drug resistance are the two inherent challenges of cisplatin which limit its application and effectiveness. Reduction of drug accumulation inside cancer cells, inactivation of drug by reacting with glutathione and metallothioneins and faster repairing of DNA lesions are responsible for cisplatin resistance. To minimize cisplatin side effects and resistance, combination therapies are used and have proven more effective to defect cancers. This article highlights a systematic description on cisplatin which includes a brief history, synthesis, action mechanism, resistance, uses, side effects and modulation of side effects. It also briefly describes development of platinum drugs from very small cisplatin complex to very large next generation nanocarriers conjugated platinum complexes.

摘要

顺铂或(SP-4-2)-二氨二氯合铂(II)是治疗各种实体瘤(如睾丸癌、卵巢癌、头颈部癌、膀胱癌、肺癌、宫颈癌、黑色素瘤、淋巴瘤等)的最有潜力和最广泛使用的药物之一。顺铂通过多种机制发挥抗癌活性,但最可接受的机制是通过与 DNA 上的嘌呤碱基相互作用生成 DNA 损伤,然后激活几种信号转导途径,最终导致细胞凋亡。然而,副作用和耐药性是顺铂固有的两个挑战,限制了其应用和效果。癌细胞内药物积累减少、与谷胱甘肽和金属硫蛋白反应使药物失活以及更快修复 DNA 损伤是导致顺铂耐药的原因。为了最大限度地减少顺铂的副作用和耐药性,联合治疗被用于治疗癌症,并已被证明比单独使用顺铂更有效。本文系统地描述了顺铂,包括其简要历史、合成、作用机制、耐药性、用途、副作用和副作用的调节。本文还简要描述了从非常小的顺铂配合物到非常大的下一代纳米载体共轭铂配合物的铂类药物的发展。

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