Transition metal chelators, pro-chelators, and ionophores as small molecule cancer chemotherapeutic agents

Chemical Society Reviews
Axel SteinbrueckJonathan L Sessler

Abstract

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 ...Continue Reading

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Citations

Aug 14, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Xiaofan TongZhigang Xie
Jan 26, 2021·Chemical Society Reviews·Juan PellicoRafael T M de Rosales
Mar 24, 2021·Metallomics : Integrated Biometal Science·Bo ChuFupei Liang
May 13, 2021·Chemical Communications : Chem Comm·Axel SteinbrueckJonathan L Sessler
Jun 10, 2021·ACS Chemical Biology·Usama AbbasiJayachandran N Kizhakkedathu
Jun 19, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Henry A AdeolaRashmi Bhardwaj
Jan 12, 2021·Journal of the American Chemical Society·Adam C SedgwickJonathan L Sessler
Dec 12, 2020·ACS Chemical Biology·Nancy WiebelhausMichael C Fitzgerald

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Methods Mentioned

BETA
xenografts
NMR
fluorescence microscopy
xenograft

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