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用于结肠癌治疗的金(III)衍生物

Gold (III) Derivatives in Colon Cancer Treatment.

作者信息

Gurba Agata, Taciak Przemysław, Sacharczuk Mariusz, Młynarczuk-Biały Izabela, Bujalska-Zadrożny Magdalena, Fichna Jakub

机构信息

Department of Pharmacodynamics, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland.

Department of Genomics, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzebiec, 05-552 Magdalenka, Poland.

出版信息

Int J Mol Sci. 2022 Jan 10;23(2):724. doi: 10.3390/ijms23020724.

Abstract

Cancer is one of the leading causes of morbidity and mortality worldwide. Colorectal cancer (CRC) is the third most frequently diagnosed cancer in men and the second in women. Standard patterns of antitumor therapy, including cisplatin, are ineffective due to their lack of specificity for tumor cells, development of drug resistance, and severe side effects. For this reason, new methods and strategies for CRC treatment are urgently needed. Current research includes novel platinum (Pt)- and other metal-based drugs such as gold (Au), silver (Ag), iridium (Ir), or ruthenium (Ru). Au(III) compounds are promising drug candidates for CRC treatment due to their structural similarity to Pt(II). Their advantage is their relatively good solubility in water, but their disadvantage is an unsatisfactory stability under physiological conditions. Due to these limitations, work is still underway to improve the formula of Au(III) complexes by combining with various types of ligands capable of stabilizing the Au(III) cation and preventing its reduction under physiological conditions. This review summarizes the achievements in the field of stable Au(III) complexes with potential cytotoxic activity restricted to cancer cells. Moreover, it has been shown that not nucleic acids but various protein structures such as thioredoxin reductase (TrxR) mediate the antitumor effects of Au derivatives. The state of the art of the in vivo studies so far conducted is also described.

摘要

癌症是全球发病和死亡的主要原因之一。结直肠癌(CRC)是男性中第三大最常被诊断出的癌症,在女性中则是第二大。包括顺铂在内的标准抗肿瘤治疗模式由于对肿瘤细胞缺乏特异性、产生耐药性以及严重的副作用而无效。因此,迫切需要治疗CRC的新方法和策略。当前的研究包括新型铂(Pt)基和其他金属基药物,如金(Au)、银(Ag)、铱(Ir)或钌(Ru)。Au(III)化合物因其与Pt(II)的结构相似性而有望成为治疗CRC的候选药物。它们的优点是在水中的溶解度相对较好,但其缺点是在生理条件下稳定性不令人满意。由于这些限制,仍在努力通过与各种能够稳定Au(III)阳离子并防止其在生理条件下还原的配体结合来改进Au(III)配合物的配方。本综述总结了具有潜在细胞毒性活性且仅限于癌细胞的稳定Au(III)配合物领域的研究成果。此外,已经表明介导Au衍生物抗肿瘤作用的不是核酸,而是各种蛋白质结构,如硫氧还蛋白还原酶(TrxR)。还描述了迄今为止进行的体内研究的现状。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aae2/8775370/34605487d59f/ijms-23-00724-g001.jpg

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