title: 9-Benzoyl 9-deazaguanines as potent xanthine oxidase inhibitors.
abstract: A novel potent xanthine oxidase inhibitor, 3-nitrobenzoyl 9-deazaguanine (LSPN451), was selected from a series of 10 synthetic derivatives. The enzymatic assays were carried out using an on-flow bidimensional liquid chromatography (2D LC) system, which allowed the screening¸ the measurement of the kinetic inhibition constant and the characterization of the inhibition mode. This compound showed a non-competitive inhibition mechanism with more affinity for the enzyme-substrate complex than for the free enzyme, and inhibition constant of 55.1±9.80 nM, about thirty times more potent than allopurinol. Further details of synthesis and enzymatic studies are presented herein.
authors.affiliation: Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Universidade Estadual de Campinas, 13148-218 Paulínia, SP, Brazil; Separare-Nucleo de Pesquisa em Cromatografia, Departamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos, SP, Brazil.
authors.forename: Marili V N
authors.initials: MV
authors.lastname: Rodrigues
authors.affiliation: Laboratório de Síntese de Produtos Naturais-LSPN, Departamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos, SP, Brazil.
authors.forename: Alexandre F
authors.initials: AF
authors.lastname: Barbosa
authors.affiliation: Laboratório de Síntese de Produtos Naturais-LSPN, Departamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos, SP, Brazil.
authors.forename: Júlia F
authors.initials: JF
authors.lastname: da Silva
authors.affiliation: Laboratório de Síntese de Produtos Naturais-LSPN, Departamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos, SP, Brazil.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: dos Santos
authors.affiliation: Separare-Nucleo de Pesquisa em Cromatografia, Departamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos, SP, Brazil.
authors.forename: Kenia L
authors.initials: KL
authors.lastname: Vanzolini
authors.affiliation: Separare-Nucleo de Pesquisa em Cromatografia, Departamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos, SP, Brazil; Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, 24020-141 Niterói, RJ, Brazil.
authors.forename: Marcela C
authors.initials: MC
authors.lastname: de Moraes
authors.affiliation: Laboratório de Síntese de Produtos Naturais-LSPN, Departamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos, SP, Brazil. Electronic address: agcorrea@ufscar.br.
authors.forename: Arlene G
authors.initials: AG
authors.lastname: Corrêa
authors.affiliation: Separare-Nucleo de Pesquisa em Cromatografia, Departamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos, SP, Brazil. Electronic address: quezia@pq.cnpq.br.
authors.forename: Quezia B
authors.initials: QB
authors.lastname: Cass
mesh_terms: D000818:Animals; D001593:Benzyl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012550:Schistosoma mansoni / Q000201:enzymology; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001593:Benzyl Compounds; D004791:Enzyme Inhibitors; C082660:9-benzyl-9-deazaguanine; D006147:Guanine; D014969:Xanthine Oxidase; D011683:Purine-Nucleoside Phosphorylase
keywords: 9-Deazaguanine; Allopurinol; Green synthesis; Microwave; Non-competitive inhibition; On-flow bidimensional liquid chromatography; Xanthine oxidase inhibitor