Synthesis and Cytoprotective Characterization of 8- Hydroxyquinoline Betti Products

Kanizsai, Iván and Madácsi, Ramóna and Hackler, László, Jr. and Szebeni, Gábor J. and Gyuris, Márió and Huzian, Orsolya and Puskás, László G. (2018) Synthesis and Cytoprotective Characterization of 8- Hydroxyquinoline Betti Products. MOLECULES, 23. p. 1934. ISSN 1420-3049


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The 8-hydroxyquinoline pharmacophore scaffold has been shown to possess a range of activities as metal chelation, enzyme inhibition, cytotoxicity, and cytoprotection. Based on our previous findings we set out to optimize the scaffold for cytoprotective activity for its potential application in central nervous system related diseases. A 48-membered Betti-library was constructed by the utilization of formic acid mediated industrial-compatible coupling with sets of aromatic primary amines such as anilines, oxazoles, pyridines, and pyrimidines, with (hetero)aromatic aldehydes and 8-hydroxiquinoline derivatives. After column chromatography and re-crystallization, the corresponding analogues were obtained in yields of 13–90%. The synthesized analogs were optimized with the utilization of a cytoprotection assay with chemically induced oxidative stress, and the most active compounds were further tested in orthogonal assays, a real time cell viability method, a fluorescence-activated cell sorting (FACS)-based assay measuring mitochondrial membrane potential changes, and gene expression analysis. The best candidates showed potent, nanomolar activity in all test systems and support the need for future studies in animal models of central nervous system (CNS) disorders.

Item Type: Article
Subjects: R Medicine / orvostudomány > RS Pharmacy and materia medica / gyógyszerészet, gyógyászati eszközök
Depositing User: Dr. Gábor János Szebeni
Date Deposited: 25 Sep 2018 06:53
Last Modified: 05 Apr 2023 07:43

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