Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824478/ https://www.ncbi.nlm.nih.gov/pubmed/27055237 http://dx.doi.org/10.1371/journal.pone.0153416 |
_version_ | 1782426099514343424 |
---|---|
author | Wehbe, Mohamed Anantha, Malathi Backstrom, Ian Leung, Ada Chen, Kent Malhotra, Armaan Edwards, Katarina Bally, Marcel B. |
author_facet | Wehbe, Mohamed Anantha, Malathi Backstrom, Ian Leung, Ada Chen, Kent Malhotra, Armaan Edwards, Katarina Bally, Marcel B. |
author_sort | Wehbe, Mohamed |
collection | PubMed |
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 of CDCs as viable candidate anticancer drugs; drugs that would represent a brand new class of therapeutics for cancer patients. |
format | Online Article Text |
id | pubmed-4824478 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-48244782016-04-22 Nanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development Wehbe, Mohamed Anantha, Malathi Backstrom, Ian Leung, Ada Chen, Kent Malhotra, Armaan Edwards, Katarina Bally, Marcel B. PLoS One Research Article 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. Public Library of Science 2016-04-07 /pmc/articles/PMC4824478/ /pubmed/27055237 http://dx.doi.org/10.1371/journal.pone.0153416 Text en © 2016 Wehbe et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Wehbe, Mohamed Anantha, Malathi Backstrom, Ian Leung, Ada Chen, Kent Malhotra, Armaan Edwards, Katarina Bally, Marcel B. Nanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development |
title | Nanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development |
title_full | Nanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development |
title_fullStr | Nanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development |
title_full_unstemmed | Nanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development |
title_short | Nanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development |
title_sort | nanoscale reaction vessels designed for synthesis of copper-drug complexes suitable for preclinical development |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824478/ https://www.ncbi.nlm.nih.gov/pubmed/27055237 http://dx.doi.org/10.1371/journal.pone.0153416 |
work_keys_str_mv | AT wehbemohamed nanoscalereactionvesselsdesignedforsynthesisofcopperdrugcomplexessuitableforpreclinicaldevelopment AT ananthamalathi nanoscalereactionvesselsdesignedforsynthesisofcopperdrugcomplexessuitableforpreclinicaldevelopment AT backstromian nanoscalereactionvesselsdesignedforsynthesisofcopperdrugcomplexessuitableforpreclinicaldevelopment AT leungada nanoscalereactionvesselsdesignedforsynthesisofcopperdrugcomplexessuitableforpreclinicaldevelopment AT chenkent nanoscalereactionvesselsdesignedforsynthesisofcopperdrugcomplexessuitableforpreclinicaldevelopment AT malhotraarmaan nanoscalereactionvesselsdesignedforsynthesisofcopperdrugcomplexessuitableforpreclinicaldevelopment AT edwardskatarina nanoscalereactionvesselsdesignedforsynthesisofcopperdrugcomplexessuitableforpreclinicaldevelopment AT ballymarcelb nanoscalereactionvesselsdesignedforsynthesisofcopperdrugcomplexessuitableforpreclinicaldevelopment |