title: Diaryl-1,2,4-oxadiazole antioxidants: synthesis and properties of inhibiting the oxidation of DNA and scavenging radicals.
abstract: Six 1,2,4-oxadiazole derivatives were prepared in order to compare their abilities to protect DNA against radical-mediated oxidation and to scavenge radicals. These derivatives had a structure based on disubstituted 1,2,4-oxadiazole, in which a vanillin group (A ring) and a substituted benzene group (B ring) were the substituents. The functional group at B ring was assigned as ortho- or meta-hydroxylbenzene group, ortho-chlorobenzene group, no group contained, and pyridine group or vanillin group at B ring. It was found that the compound with two vanillin groups attaching to oxadiazole can trap 2.05 radicals in protecting DNA against 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation, and the compound with an ortho-hydroxylbenzene group at B ring can trap 1.78 radicals. The compound with an ortho-chlorobenzene group at B ring exhibited the highest ability to inhibit (·)OH-induced oxidation of DNA, while the compound with a meta-hydroxylbenzene group at B ring inhibited Cu(2+)/glutathione (GSH)-induced oxidation of DNA efficiently. The ortho- and para-hydroxylbenzene groups at B ring made the compounds possess the highest rate constant (k) in scavenging 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(+.)) and 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH). Therefore, only a few hydroxyl groups can markedly enhance the activity of the core-branched antioxidant, which may be a novel structural feature in designing antioxidant.
authors.affiliation: Department of Organic Chemistry, College of Chemistry, Jilin University, No. 2519 Jiefang Road, Changchun 130021, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.forename: Zai-Qun
authors.initials: ZQ
authors.lastname: Liu
mesh_terms: D000578:Amidines / Q000494:pharmacology; D052160:Benzothiazoles / Q000737:chemistry; D001713:Biphenyl Compounds / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D004247:DNA / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005609:Free Radicals / Q000737:chemistry; D005978:Glutathione / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000494:pharmacology; D007700:Kinetics; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010851:Picrates / Q000737:chemistry; D013451:Sulfonic Acids / Q000737:chemistry
chemical_list: D000578:Amidines; D052160:Benzothiazoles; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D005609:Free Radicals; D010069:Oxadiazoles; D010851:Picrates; D013451:Sulfonic Acids; C002502:2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; D017665:Hydroxyl Radical; C046728:2,2'-azobis(2-amidinopropane); D004247:DNA; C004931:1,1-diphenyl-2-picrylhydrazyl; D005978:Glutathione