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Nanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development

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 complexatio... Full description

Journal Title: PLoS One Apr 2016, Vol.11(4), p.e0153416
Main Author: Wehbe, Mohamed
Other Authors: Backstrom, Ian , Leung, Ada , Chen, Kent , Malhotra, Armaan , Edwards, Katarina , Bally, Marcel
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 19326203 ; DOI: 10.1371/journal.pone.0153416
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title: Nanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development
format: Article
creator:
  • Wehbe, Mohamed
  • Backstrom, Ian
  • Leung, Ada
  • Chen, Kent
  • Malhotra, Armaan
  • Edwards, Katarina
  • Bally, Marcel
subjects:
  • Laboratories
  • Cancer
  • Liposomes
  • Clioquinol
  • Alcoholism
  • Cancer
  • Cytotoxicity
  • Copper
  • Antitumor Activity
  • Drugs
  • Copper
  • Drug Abuse
  • Research & Development–R&D
  • Drug Development
  • Cancer
  • Alcoholism
  • Alzheimers Disease
ispartof: PLoS One, Apr 2016, Vol.11(4), p.e0153416
description: 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...
language: eng
source:
identifier: E-ISSN: 19326203 ; DOI: 10.1371/journal.pone.0153416
fulltext: fulltext_linktorsrc
issn:
  • 19326203
  • 1932-6203
url: Link


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titleNanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development
creatorWehbe, Mohamed ; Backstrom, Ian ; Leung, Ada ; Chen, Kent ; Malhotra, Armaan ; Edwards, Katarina ; Bally, Marcel
ispartofPLoS One, Apr 2016, Vol.11(4), p.e0153416
identifierE-ISSN: 19326203 ; DOI: 10.1371/journal.pone.0153416
subjectLaboratories ; Cancer ; Liposomes ; Clioquinol ; Alcoholism ; Cancer ; Cytotoxicity ; Copper ; Antitumor Activity ; Drugs ; Copper ; Drug Abuse ; Research & Development–R&D ; Drug Development ; Cancer ; Alcoholism ; Alzheimers Disease
descriptionThe 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...
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descriptionThe 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...
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titleNanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development
authorWehbe, Mohamed ; Backstrom, Ian ; Leung, Ada ; Chen, Kent ; Malhotra, Armaan ; Edwards, Katarina ; Bally, Marcel
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6Copper
7Antitumor Activity
8Drugs
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10Research & Development–R&D
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12Alzheimers Disease
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abstractThe 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...
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