Synthesis and Cytoprotective Characterization of 8-Hydroxyquinoline Betti Products
AbstractThe 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. View Full-Text
- Supplementary File 1:
PDF-Document (PDF, 10409 KB)
Share & Cite This Article
Kanizsai, I.; Madácsi, R.; Hackler Jr., L.; Gyuris, M.; Szebeni, G.J.; Huzián, O.; Puskás, L.G. Synthesis and Cytoprotective Characterization of 8-Hydroxyquinoline Betti Products. Molecules 2018, 23, 1934.
Kanizsai I, Madácsi R, Hackler Jr. L, Gyuris M, Szebeni GJ, Huzián O, Puskás LG. Synthesis and Cytoprotective Characterization of 8-Hydroxyquinoline Betti Products. Molecules. 2018; 23(8):1934.Chicago/Turabian Style
Kanizsai, Iván; Madácsi, Ramóna; Hackler Jr., László; Gyuris, Márió; Szebeni, Gábor J.; Huzián, Orsolya; Puskás, László G. 2018. "Synthesis and Cytoprotective Characterization of 8-Hydroxyquinoline Betti Products." Molecules 23, no. 8: 1934.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.