INVESTIGADORES
MOYANO Elizabeth Laura
artículos
Título:
Identification of pyrazolotriazinones as potential agents for hyperuricemia treatment by using in vitro and in silico studies
Autor/es:
SCIÚ, M. LOURDES; SANTI, M. DANIELA; CANTERO, JORGE; COLOMER, JUAN P.; PAULINO-ZUNINI, MARGOT; ORTEGA, M. GABRIELA; MOYANO, E. LAURA
Revista:
SN Applied Sciences
Editorial:
Springer
Referencias:
Año: 2020 vol. 2 p. 1298 - 1311
ISSN:
2523-3963
Resumen:
Heterocyclic compounds structurally related to purine bases have been described as anticonvulsants, antifungal, antiviral,anticancer, enzyme inhibitors, among others. In this work, pyrazolo[3,4-d][1-3]triazin-4-ones (2) and pyrazolo[4,3-d][1-3]triazin-4-ones (3) derivatives were evaluated as xanthine oxidase (XO) inhibitors. Compounds 3 showed the best activitywith IC50 values range of 0.9?2.9 µM. While the inhibition performance of pyrazolotriazinones was not more active thanreference inhibitor allopurinol (IC50=0.247±0.004) µM, these nuclei provide a platform for new and more potent XOinhibitors. Accordingly, molecular modeling methods were carried out to understand the compounds-enzyme bindingmode. First, we have performed a qualitative SAR study using the MOE? SAR tool. This study showed three commonscafolds and the most active was identifed. These results are certainly valuable and will be taken into account in futuresynthesis of structurally related compounds. Furthermore, QSAR 2D and 3D studies were performed and structuralrequirements for the activity are reported. The obtained results led us to present the structural improvements for therational design and synthesis of new pyrazolotriazinone derivatives with greater xanthine oxidase inhibitory activitythan allopurinol.