title: α-Aryl-N-aryl nitrones: Synthesis and screening of a new scaffold for cellular protection against an oxidative toxic stimulus.
abstract: Nitrone-containing compounds are commonly employed as spin traps of free radical species in chemical and biological studies. Some molecules as α-phenyl-N-t-butyl nitrone (PBN) and its derivatives have been tested as potential drugs to treat oxidative stress related diseases, as Alzheimer and stroke for example. In this work we report the design and the synthesis of α-aryl-N-aryl nitrones and their cytoprotection profile on human neuroblastoma cells (SH-SY5Y) under induced oxidative stress. All the nine synthesized nitrones showed a significant response at low micromolar concentration. The selected compound 8 (α-phenyl-N-phenyl nitrone) increased the reduced glutathione (GSH) levels by 65% and lowered the necrotic cell death from 25.8% to 3.8%. Based on our data, the designed highly conjugated nitrone double-bond skeleton can be considered as a good scaffold for further studies regarding oxidative stress-related diseases.
authors.affiliation: Center for Natural Science and Humanities, Federal University of ABC-CCNH, UFABC, Avenida dos Estados, 5001, S610-3-Tower A, 09210-580 Santo Andre, SP, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Matias
authors.affiliation: Center for Natural Science and Humanities, Federal University of ABC-CCNH, UFABC, Avenida dos Estados, 5001, S610-3-Tower A, 09210-580 Santo Andre, SP, Brazil.
authors.forename: G
authors.initials: G
authors.lastname: Biazolla
authors.affiliation: Center for Natural Science and Humanities, Federal University of ABC-CCNH, UFABC, Avenida dos Estados, 5001, S610-3-Tower A, 09210-580 Santo Andre, SP, Brazil.
authors.forename: G
authors.initials: G
authors.lastname: Cerchiaro
authors.affiliation: Center for Natural Science and Humanities, Federal University of ABC-CCNH, UFABC, Avenida dos Estados, 5001, S610-3-Tower A, 09210-580 Santo Andre, SP, Brazil. Electronic address: artur.keppler@ufabc.edu.br.
authors.forename: A F
authors.initials: AF
authors.lastname: Keppler
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects*; D012545:Schiff Bases / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000814:Aniline Compounds; D000975:Antioxidants; D012545:Schiff Bases; C000609882:alpha-phenyl-N-phenyl nitrone
keywords: Cytoprotection; Nitrone; Oxidative stress; SH-SY5Y; Synthesis