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Transition metal chelators, pro-chelators, and ionophores as small molecule cancer chemotherapeutic agents
- Source :
- Chemical Society Reviews. 49:3726-3747
- Publication Year :
- 2020
- Publisher :
- Royal Society of Chemistry (RSC), 2020.
-
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 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.
- Subjects :
- Dose limiting toxicity
Ionophores
010405 organic chemistry
business.industry
Cancer
Antineoplastic Agents
General Chemistry
Drug resistance
010402 general chemistry
medicine.disease
01 natural sciences
Small molecule
0104 chemical sciences
Coordination Complexes
Cancer stem cell
Neoplasms
Cancer cell
Transition Elements
Cancer research
Humans
Medicine
Treatment resistance
business
Cytotoxicity
Chelating Agents
Subjects
Details
- ISSN :
- 14604744 and 03060012
- Volume :
- 49
- Database :
- OpenAIRE
- Journal :
- Chemical Society Reviews
- Accession number :
- edsair.doi.dedup.....2ae164b8b24800d1bc00602cee79a571