Please use this identifier to cite or link to this item:
|Title:||Effect of Structural Modifications to Glyoxal-bis(thiosemicarbazonato)copper(II) Complexes on Cellular Copper Uptake, Copper-Mediated ATP7A Trafficking, and P-Glycoprotein Mediated Efflux.||Austin Authors:||Acevedo, Karla M;Hayne, David J;McInnes, Lachlan E;Noor, Asif;Duncan, Clare;Moujalled, Diane;Volitakis, Irene;Rigopoulos, Angela;Barnham, Kevin J;Villemagne, Victor L ;White, Anthony R;Donnelly, Paul S||Affiliation:||Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Molecular Imaging and Therapy, Centre for PET, Austin Health, Heidelberg, Victoria, Australia
|Issue Date:||8-Feb-2018||metadata.dc.date:||2018-01-08||Publication information:||Journal of medicinal chemistry 2018; 61(3): 711-723||Abstract:||Bis(thiosemicarbazonato)copper(II) complexes are of interest as potential therapeutics for cancer and neurodegenerative diseases as well as imaging agents for positron emission tomography (PET). The cellular uptake of six bis(thiosemcarbazonato)copper(II)complexes derived from glyoxal, with different functional groups Cu(gtsx) where x = different functional groups, was investigated in SKOV-3, HEK293, and HEK293 P-gp cell lines. Treatment of the cells with the copper complexes increased intracellular copper and increased levels of p-ERK due to activation of the Ras-Raf-MEK-ERK pathway. Treatment of SKOV-3 cells with low concentrations (μM) of two of the copper complexes led to trafficking of the endogenous copper transporter ATP7A from the Golgi network to the cell membrane. Experiments in HEK293 and HEK293-P-gp cells suggest that Cu(gtsm) and Cu(gtse) are substrates for the P-gp efflux protein but the complex with a pyrrolidine functional group, Cu(gtspyr), is not. A PET experiment in mice showed that [64Cu]Cu(gtspyr) has reasonable brain uptake but high liver uptake.||URI:||http://ahro.austin.org.au/austinjspui/handle/1/19352||DOI:||10.1021/acs.jmedchem.7b01158||ORCID:||0000-0001-5373-0080||PubMed URL:||29232129||Type:||Journal Article|
|Appears in Collections:||Journal articles|
Show full item record
checked on Dec 4, 2022
Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.