Viola-Rhenals Maricela, Patel Kush R, Jaimes-Santamaria Laura, Wu Guojun, Liu Jinbao, Dou Q Ping
Biochemistry and Cell Biology of Cancer Group, Exacts and Natural Science Faculty, University of Cartagena, Cartagena, Colombia.
Barbara Ann Karmanos Cancer Institute, Departments of Oncology, Pharmacology and Pathology, School of Medicine, Wayne State University, Detroit, United States.
Curr Med Chem. 2018 Feb 12;25(4):506-524. doi: 10.2174/0929867324666171023161121.
Considerable evidence demonstrates the importance of dithiocarbamates especially disulfiram as anticancer drugs. However there are no systematic reviews outlining how their metal-binding ability is related to their anticancer activity. This review aims to summarize chemical features and metal-binding activity of disulfiram and its metabolite DEDTC, and discuss different mechanisms of action of disulfiram and their contributions to the drug's anticancer activity.
We undertook a disulfiram-related search on bibliographic databases of peerreviewed research literature, including many historic papers and in vitro, in vivo, preclinical and clinical studies. The selected papers were carefully reviewed and summarized.
More than five hundreds of papers were obtained in the initial search and one hundred eighteen (118) papers were included in the review, most of which deal with chemical and biological aspects of Disulfiram and the relationship of its chemical and biological properties. Eighty one (81) papers outline biological aspects of dithiocarbamates, and fifty seven (57) papers report biological activity of Disulfiram as an inhibitor of proteasomes or inhibitor of aldehyde dehydrogenase enzymes, interaction with other anticancer drugs, or mechanism of action related to reactive oxygen species. Other papers reviewed focus on chemical aspects of dithiocarbamates.
This review confirms the importance of chemical features of compounds such as Disulfiram to their biological activities, and supports repurposing DSF as a potential anticancer agent.
大量证据表明二硫代氨基甲酸盐尤其是双硫仑作为抗癌药物的重要性。然而，尚无系统综述概述它们的金属结合能力与其抗癌活性之间的关系。本综述旨在总结双硫仑及其代谢产物二乙胺基二硫代甲酸盐（DEDTC）的化学特征和金属结合活性，并讨论双硫仑的不同作用机制及其对该药物抗癌活性的贡献。
我们在同行评审研究文献的书目数据库中进行了与双硫仑相关的搜索，包括许多历史文献以及体外、体内、临床前和临床研究。对所选论文进行了仔细审查和总结。
在初步搜索中获得了五百多篇论文，本综述纳入了一百一十八（118）篇论文，其中大部分涉及双硫仑的化学和生物学方面及其化学和生物学性质的关系。八十一（81）篇论文概述了二硫代氨基甲酸盐的生物学方面，五十七（57）篇论文报道了双硫仑作为蛋白酶体抑制剂或乙醛脱氢酶抑制剂的生物学活性、与其他抗癌药物的相互作用或与活性氧相关的作用机制。其他综述论文聚焦于二硫代氨基甲酸盐的化学方面。
本综述证实了双硫仑等化合物的化学特征对其生物学活性的重要性，并支持将双硫仑重新用作潜在的抗癌药物。
