文献类型：期刊文献

英文题名：Transition metal chelators, pro-chelators, and ionophores as small molecule cancer chemotherapeutic agents

作者：Steinbrueck, Axel[1];Sedgwick, Adam C.[1];Brewster, James T., II[1];Yan, Kai-Cheng[2,3];Shang, Ying[2,3];Knoll, Daniel M.[1];Vargas-Zuniga, Gabriela I.[1];He, Xiao-Peng[2,3];Tian, He[2,3];Sessler, Jonathan L.[1]

机构：[1]Univ Texas Austin, Dept Chem, Austin, TX 78712 USA;[2]East China Univ Sci & Technol, Sch Chem & Mol Engn, Feringa Nobel Prize Scientist Joint Res Ctr, Key Lab Adv Mat, 130 Meilong Rd, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Sch Chem & Mol Engn, Feringa Nobel Prize Scientist Joint Res Ctr, Joint Int Res Lab Precis Chem & Mol Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2020

卷号：49

期号：12

起止页码：3726

外文期刊名：CHEMICAL SOCIETY REVIEWS

收录：;EI(收录号：20203809192970);WOS:【SCI-EXPANDED(收录号:WOS:000545009500011)】；

基金：The work in Austin was supported by the National Institutes of Health (R01 CA 68682 to J. L. S.) and the Robert A. Welch Foundation (F-0018 to J. L. S.). The work at ECUST was supported by the NSFC (21788102 and 21722801), The National Key Sci-Tech Special Projects of Infection Diseases of China (2018ZX10732202), Shanghai Municipal Science and Technology Major Project (2018SHZDZX03), and the International Cooperation Program of Shanghai Science and Technology Committee (17520750100).

语种：英文

外文关键词：Chelation - Cytology - Drug interactions - Stem cells - Tumors - Zinc - Expansion - Diseases

摘要：Cancer is among the leading causes of death worldwide. Although a number of new treatment options have been developed in recent years, there remains a need for improved chemotherapies. The primary challenges facing new cancer drugs include: (1) improving patient quality of life, (2) overcoming drug resistance and (3) lowering reoccurrence rates. Major drawbacks of current chemotherapeutics arise from poor selectivity towards cancer cells, dose limiting toxicities, compliance-reducing side effects, and an inability to address resistance mechanisms. Chemotherapeutics that fail to achieve complete eradication of the disease can also lead to relapse and promote treatment resistance. New strategies to overcome these drawbacks include the use of transition metal chelators and ionophores to alter selectively the concentrations of iron, copper, and zinc in cancer cells. A number of metal chelators have successfully demonstrated cytotoxicity and targeted activity against drug-resistant cancer cells; several have proved effective against cancer stem cells, a significant cause of tumour reoccurrence. However, problems with formulation and targeting have been noted. Recent efforts have thus focused on the design of pro-chelators, inactive versions of chelators that are designed to be activated in the tumour. This is an appealing strategy that may potentially increase efficacy towards cancer-resistant malignant cells. This Tutorial Review summarizes recent progress involving transition metal chelators, pro-chelators, and ionophores as potential cancer chemotherapeutics. We will focus on the reported agents that are able to coordinate iron, copper, and zinc.