9-Benzoyl 9-deazaguanines as potent xanthine oxidase inhibitors

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• 作者：Marili V.N. Rodrigues^a ; ^b ; Alexandre F. Barbosa^c ; J&uacute ; lia F. da Silva^c ; Deborah A. dos Santos^c ; Kenia L. Vanzolini^b ; Marcela C. de Moraes^b ; ^d ; Arlene G. Corrê ; a^c ; ^{agcorrea@ufscar.br" class="auth_mail" title="E-mail the corresponding author} ; Quezia B. Cass^b ; ^{quezia@pq.cnpq.br" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Xanthine oxidase inhibitor ; 9-Deazaguanine ; On-flow bidimensional liquid chromatography ; Non-competitive inhibition ; Allopurinol ; Green synthesis ; Microwave
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：15 January 2016
• 年：2016
• 卷：24
• 期：2
• 页码：226-231
• 全文大小：516 K

文摘

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.