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Nanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development
- Source :
- PLoS ONE, PLoS ONE, Vol 11, Iss 4, p e0153416 (2016)
- Publication Year :
- 2016
- Publisher :
- Uppsala universitet, Analytisk kemi, 2016.
-
Abstract
- The development of copper-drug complexes (CDCs) is hindered due to their very poor aqueous solubility. Diethyldithiocarbamate (DDC) is the primary metabolite of disulfiram, an approved drug for alcoholism that is being repurposed for cancer. The anticancer activity of DDC is dependent on complexation with copper to form copper bis-diethyldithiocarbamate (Cu(DDC)(2)), a highly insoluble complex that has not been possible to develop for indications requiring parenteral administration. We have resolved this issue by synthesizing Cu(DDC)(2) inside liposomes. DDC crosses the liposomal lipid bilayer, reacting with the entrapped copper; a reaction that can be observed through a colour change as the solution goes from a light blue to dark brown. This method is successfully applied to other CDCs including the anti-parasitic drug clioquinol, the natural product quercetin and the novel targeted agent CX-5461. Our method provides a simple, transformative solution enabling, for the first time, the development of CDCs as viable candidate anticancer drugs; drugs that would represent a brand new class of therapeutics for cancer patients.
- Subjects :
- 0301 basic medicine
Annan kemi
Cancer Treatment
lcsh:Medicine
Biochemistry
Antioxidants
chemistry.chemical_compound
Mice
0302 clinical medicine
Drug Metabolism
Neoplasms
Tumor Cells, Cultured
Macromolecular Structure Analysis
Medicine and Health Sciences
Nanotechnology
Solubility
lcsh:Science
media_common
Liposome
Multidisciplinary
Lipid Analysis
integumentary system
Clioquinol
Lipids
3. Good health
Chemistry
Oncology
030220 oncology & carcinogenesis
Physical Sciences
Female
Quercetin
Cellular Structures and Organelles
Ditiocarb
medicine.drug
Research Article
Chemical Elements
Drug
Cell Survival
media_common.quotation_subject
Materials Science
Material Properties
Antineoplastic Agents
Approved drug
03 medical and health sciences
medicine
Animals
Humans
Pharmacokinetics
Benzothiazoles
Vesicles
Naphthyridines
Molecular Biology
Pharmacology
Natural product
lcsh:R
fungi
Biology and Life Sciences
Cell Biology
Combinatorial chemistry
Xenograft Model Antitumor Assays
030104 developmental biology
chemistry
Disulfiram
Liposomes
lcsh:Q
Other Chemistry Topics
Drug metabolism
Copper
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, PLoS ONE, Vol 11, Iss 4, p e0153416 (2016)
- Accession number :
- edsair.doi.dedup.....413cb2ee31a1dd4550c94d3556bc62c3