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近年来,金(I)和金(III)配合物作为癌症治疗药物的发展。

Recent development of gold(I) and gold(III) complexes as therapeutic agents for cancer diseases.

机构信息

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

Institute of Pharmacy/Pharmaceutical Chemistry, University of Innsbruck, Center for Chemistry and Biomedicine, Innsbruck, Austria.

出版信息

Chem Soc Rev. 2022 Jul 4;51(13):5518-5556. doi: 10.1039/d1cs00933h.

Abstract

Metal complexes have demonstrated significant antitumor activities and platinum complexes are well established in the clinical application of cancer chemotherapy. However, the platinum-based treatment of different types of cancers is massively hampered by severe side effects and resistance development. Consequently, the development of novel metal-based drugs with different mechanism of action and pharmaceutical profile attracts modern medicinal chemists to design and synthesize novel metal-based agents. Among non-platinum anticancer drugs, gold complexes have gained considerable attention due to their significant antiproliferative potency and efficacy. In most situations, the gold complexes exhibit anticancer activities by targeting thioredoxin reductase (TrxR) or other thiol-rich proteins and enzymes and trigger cell death reactive oxygen species (ROS). Interestingly, gold complexes were recently reported to elicit biochemical hallmarks of immunogenic cell death (ICD) as an ICD inducer. In this review, the recent progress of gold(I) and gold(III) complexes is comprehensively summarized, and their activities and mechanism of action are documented.

摘要

金属配合物已表现出显著的抗肿瘤活性,铂配合物在癌症化疗的临床应用中已得到充分证实。然而,由于严重的副作用和耐药性的发展,不同类型癌症的铂类治疗受到了极大的阻碍。因此,开发具有不同作用机制和药物特征的新型金属药物引起了现代药物化学家的兴趣,以设计和合成新型金属药物。在非铂类抗癌药物中,金配合物因其显著的增殖抑制作用和疗效而受到广泛关注。在大多数情况下,金配合物通过靶向硫氧还蛋白还原酶(TrxR)或其他富含巯基的蛋白质和酶来发挥抗癌活性,并触发细胞死亡和活性氧(ROS)。有趣的是,最近有报道称金配合物作为免疫原性细胞死亡(ICD)诱导剂,可引起免疫原性细胞死亡(ICD)的生化特征。在这篇综述中,全面总结了金(I)和金(III)配合物的最新进展,并记录了它们的活性和作用机制。

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