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金诺芬及其类似物作为治疗结直肠癌的潜在药物。

Auranofin and its analogs as prospective agents for the treatment of colorectal cancer.

作者信息

Massai Lara, Cirri Damiano, Marzo Tiziano, Messori Luigi

机构信息

Department of Chemistry, University of Florence, Sesto Fiorentino 50019, Italy.

Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa 56124, Italy.

出版信息

Cancer Drug Resist. 2022 Jan 4;5(1):1-14. doi: 10.20517/cdr.2021.71. eCollection 2022.

Abstract

Today colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. This disease is poorly chemo-sensitive toward the existing medical treatments so that new and more effective therapeutic agents are urgently needed and intensely sought. Platinum drugs, oxaliplatin in particular, were reported to produce some significant benefit in CRC treatment, triggering the general interest of medicinal chemists and oncologists for metal-based compounds as candidate anti-CRC drugs. Within this frame, gold compounds and, specifically, the established antiarthritic drug auranofin with its analogs, form a novel group of promising anticancer agents. Owing to its innovative mechanism of action and its favorable pharmacological profile, auranofin together with its derivatives are proposed here as novel experimental agents for CRC treatment, capable of overcoming resistance to platinum drugs. Some encouraging results in this direction have already been obtained. A few recent studies demonstrate that the action of auranofin may be further potentiated through the preparation of suitable pharmaceutical formulations capable of protecting the gold pharmacophore from unselective reactivity or through the design of highly synergic drug combinations. The perspectives of the research in this field are outlined.

摘要

如今,结直肠癌(CRC)是全球癌症死亡的主要原因之一。这种疾病对现有医学治疗的化疗敏感性较差,因此迫切需要并积极寻找新的、更有效的治疗药物。据报道,铂类药物,尤其是奥沙利铂,在CRC治疗中产生了一些显著疗效,引发了药物化学家与肿瘤学家对金属基化合物作为候选抗CRC药物的普遍关注。在此背景下,金化合物,特别是已确立的抗关节炎药物金诺芬及其类似物,构成了一类新型的有前景的抗癌剂。由于其创新的作用机制和良好的药理学特性,金诺芬及其衍生物在此被提议作为CRC治疗的新型实验药物,能够克服对铂类药物的耐药性。在这个方向上已经取得了一些令人鼓舞的结果。最近的一些研究表明,通过制备能够保护金药效基团免受非选择性反应的合适药物制剂,或者通过设计高度协同的药物组合,金诺芬的作用可能会进一步增强。本文概述了该领域的研究前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b75e/8992591/73924dc1bcce/cdr-5-1.fig.1.jpg

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