Clioquinol, a lipophilic Zn2+ chelator, augments and attenuates the cytotoxicity of H2O2: a bell-shaped response curve of the effects of the drug

Insight into inhibition of the human amyloid beta protein precursor (APP: PDB ID 3UMI) using (E)-N-(pyridin-2-ylmethylene)arylamine (LR) models: structure elucidation of a family of ZnX2-LRcomplexes

“…44 In an another endeavour, a penta-coordinated structural model for Zn-Aβ (1-28) was proposed, where the Zn is coordinated by the N-terminal NH 2 group of Asp 1 and three nitrogen atoms of the histidines (His 6, His 13 and His 14), and the carboxylate oxygen atom of Glu 11, in a micellar solution at biological pH. In this context, the Zn binding fragment of Aβ has been studied using QM/MM (hybrid quantum mechanics/ molecular mechanics) calculations by applying the initial geometry, the metal ion and the side chains of His 6, His 13, His 14 and Glu 11 of the reported NMR solution structure by Zirah et al 43 These calculations confirmed that the three histidines and Glu 11 of Aβ (1-16) and Aβ (6)(7)(8)(9)(10)(11)(12)(13)(14) are involved in coordination with the Zn atom. In this context, the Zn binding fragment of Aβ has been studied using QM/MM (hybrid quantum mechanics/ molecular mechanics) calculations by applying the initial geometry, the metal ion and the side chains of His 6, His 13, His 14 and Glu 11 of the reported NMR solution structure by Zirah et al 43 These calculations confirmed that the three histidines and Glu 11 of Aβ (1-16) and Aβ (6)(7)(8)(9)(10)(11)(12)(13)(14) are involved in coordination with the Zn atom.…”

“…45 Despite the encouraging results derived from NMR, computational studies were also performed for the clarification of metal interactions with Aβ and to find correlation between theory/computation and experiment for understanding the structures of metal-Aβ complexes. In this context, the Zn binding fragment of Aβ has been studied using QM/MM (hybrid quantum mechanics/ molecular mechanics) calculations by applying the initial geometry, the metal ion and the side chains of His 6, His 13, His 14 and Glu 11 of the reported NMR solution structure by Zirah et al 43 These calculations confirmed that the three histidines and Glu 11 of Aβ (1-16) and Aβ (6)(7)(8)(9)(10)(11)(12)(13)(14) are involved in coordination with the Zn atom. Molecular dynamics simulations of Zn/Aβ models reveal that the zinc ions can coordinate Aβ simultaneously both intramolecularly and intermolecularly, and hence facilitate Aβ aggregation.…”

“…Among the chelators tested so far, clioquinol (5-chloro-7-iodoquinolin-8-ol) and Cu-chelating oxine based analogue PBT2 (5,7-dichloro-2-((dimethylamino)methyl)quinolin-8-ol) have entered phase II and phase IIa clinical trials, respectively, while other chelators are under development as several issues pertaining to the mechanism/mode of action are unsettled. [12][13][14][15] However, research studies paved the way to the design and preparation of new drugs for AD therapy.…”

Multifunctional Supramolecular Vesicles as Zn2+‐Triggered Microglial Modulator Alleviates Alzheimer's Disease

“…[ 8 ] Accordingly, Zn 2+ ‐chelators exhibit great potential in inhibiting Aβ cytotoxicity and Oxidative stress. [ 9 ] Nevertheless, the deteriorate processes is continuing forward with damaged microglia. [ 10 ] Modulating the function of damaged microglia from a further upstream should be taken into account in AD treatment.…”