PBT2 acts through a different mechanism of action than other 8-hydroxyquinolines: an X-ray fluorescence imaging study

Abstract

8-Hydroxyquinolines (8HQs) comprise a family of metal-binding compounds that have been used or tested for use in numerous medicinal applications, including as treatments for bacterial infection, Alzheimer’s disease, and cancer....

Selective Targeting of Cancer Cells by Copper Ionophores: An Overview

“…In addition to methods for the safe vehiculation of CQ, the researchers have studied other HQ derivatives that could have a greater efficacy as anticancer agents and reduced side effects. Just a few examples include 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline (PBT2) and nitroxoline that are more active compared to CQ in inhibiting cancer cell proliferation in the presence of Cu (Jiang et al, 2011;Summers et al, 2020). This improved activity could be related to a different mechanism of action or a different cellular Cu distribution (Summers et al, 2020).…”

“…Just a few examples include 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline (PBT2) and nitroxoline that are more active compared to CQ in inhibiting cancer cell proliferation in the presence of Cu (Jiang et al, 2011;Summers et al, 2020). This improved activity could be related to a different mechanism of action or a different cellular Cu distribution (Summers et al, 2020).…”

Atomic spectrometry update – a review of advances in X-ray fluorescence spectrometry and its special applications

“…Also in the context of cancer research, Summers et al 26 investigated the intracellular distribution of selected elements in rat brain glioma cells following 8HQ-treatment with and without Cu II co-treatments. When Cu II was added, all three 8HQ compounds investigated demonstrated greater cytotoxicity towards cancer cells.…”

Evaluation of Copper Chelation Therapy in a Transgenic Rat Model of Cerebral Amyloid Angiopathy

“…X-ray fluorescence microscopy (XFM) is a widely used technique for imaging the distribution and concentration of trace elements in biological cells and tissues. − For example, XFM has recently been used to study the effect of chelation therapy on the distribution of copper in a mouse model of Wilson’s disease, the mechanism of copper redistribution in cells by 8-hydroxyquinolines, and the effect of Zn supplementation on brain copper deposition in a tau mouse model of AD . Previously, we showed by XFM that a higher copper content is present in cerebral vascular amyloid deposits compared to parenchymal plaques .…”