9-Benzoyl 9-deazaguanines as potent xanthine oxidase inhibitors.

Authors :: Rodrigues MV
Barbosa AF
da Silva JF
dos Santos DA
Vanzolini KL
de Moraes MC
Corrêa AG
Cass QB
Source :: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2016 Jan 15; Vol. 24 (2), pp. 226-31. Date of Electronic Publication: 2015 Dec 08.
Publication Year :: 2016
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.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)