Recent progress in multifunctional metal chelators as potential drugs for Alzheimer's disease

Multitarget trehalose-carnosine conjugates inhibit Aβ aggregation, tune copper(II) activity and decrease acrolein toxicity

“…[68] These "multitarget" directed ligands (MTDL) are intended to prevent AD symptoms as well as disease progression as opposed to traditional therapies that were solely based on cholinesterase inhibition. [69,70] Reviews of MTDL classify the new molecules based on one chemical lead and list the modifications that might be introduced to maximize the pharmacological parameters measured for a given compound. [ 71 ] The newly synthesized Car derivative falls in this class of compounds as it may cope with: i) Aβ fibril formation, including also metal-assisted fibril formation; ii) alteration of metal homeostasis; iii) ROS activities and iv) ACR toxicity.…”

Cyclodextrins 3‐Functionalized with 8‐Hydroxyquinolines: Copper‐Binding Ability and Inhibition of Synuclein Aggregation

“…Ar ecent pharmacological approachf or these diseases has involved the application of molecules able to compete with amyloidogenic peptides for the metal ions and/or to restore metal homeostasis. [9] Among them, 8-hydroxyquinolines (HQs) are reported to have ah igh interestf or the treatment of PD and AD. [10] Whereas metal-binding agents such as PBT2 are in clinical trials for PD and other neurodegeneratived isorders, this and other HQs are currently under investigation in in vitro and in vivo systems to determine the mode of action in various diseases.…”

A Metallo Pro‐Drug to Target CuII in the Context of Alzheimer's Disease

“…1 + was shown to efficiently limit superoxide flow in activated macrophages [14] and to limit inflammation with a potential intracellular SOD-activity, while the ligand alone (LH) showed a cellular toxicity. [15] In the present communication, we used complex 1 + instead of following a classical chelating strategy [16] and using a free ligand that might be toxic. Furthermore in the context of AD, the importance of oxidative stress is widely acknowledged, [3] proving relevant the use of a SOD mimict.…”