514185-07-0Relevant articles and documents
Novel 8-Hydroxyquinoline Derivatives as Multitarget Compounds for the Treatment of Alzheimer′s Disease
Prati, Federica,Bergamini, Christian,Fato, Romana,Soukup, Ondrej,Korabecny, Jan,Andrisano, Vincenza,Bartolini, Manuela,Bolognesi, Maria Laura
, p. 1284 - 1295 (2016)
We discovered a small series of hit compounds that show multitargeting activities against key targets in Alzheimer′s disease (AD). The compounds were designed by combining the structural features of the anti-AD drug donepezil with clioquinol, which is able to chelate redox-active metals, thus decreasing metal-driven oxidative phenomena and β-amyloid (Aβ)-mediated neurotoxicity. The majority of the new hybrid compounds selectively target human butyrylcholinesterase at micromolar concentrations and effectively inhibit Aβ self-aggregation. In addition, compounds 5-chloro-7-((4-(2-methoxybenzyl)piperazin-1-yl)methyl)-8-hydroxyquinoline (1 b), 7-((4-(2-methoxybenzyl)piperazin-1-yl)methyl)-8-hydroxyquinoline (2 b), and 7-(((1-benzylpiperidin-4-yl)amino)methyl)-5-chloro-8-hydroxyquinoline (3 a) are able to chelate copper(II) and zinc(II) and exert antioxidant activity in vitro. Importantly, in the case of 2 b, the multitarget profile is accompanied by high predicted blood–brain barrier permeability, low cytotoxicity in T67 cells, and acceptable toxicity in HUVEC primary cells.
Synthesis and structure-activity relationship study of 8-hydroxyquinoline- derived Mannich bases as anticancer agents
Shaw, Arthur Y.,Chang, Chun-Yi,Hsu, Mei-Yuan,Lu, Pei-Jung,Yang, Chia-Ning,Chen, Hui-Ling,Lo, Cheng-Wei,Shiau, Chung-Wai,Chern, Ming-Kai
experimental part, p. 2860 - 2867 (2010/08/20)
To continue our early study on the structural modifications of clioquinol, more 8-hydroxyquinoline-derived Mannich bases were synthesized and examined for growth-inhibitory effect. Taken Mannich base 1 as our lead compound, upon replacement of either sulfonyl group with methylene group or piperazine ring with ethylenediamine group resulted in an appreciable increase in potency. On the other hand, as 8-hydroxyquinoline was replaced with phenol, 3-hydroxypyridine and 1-naphthol, a dramatic decrease in activity was observed, indicating that 8-hydroxyquinoline is a crucial scaffold for activity. Further 3D-QSAR analysis on HeLa cells revealed that both steric and electronic effects contributed equally to growth inhibition. Taken together, the structure-activity relationships obtained from both in vitro data and CoMFA model warrant a valuable reference for further study.
