Identification of pyrazolotriazinones as potential agents for hyperuricemia treatment by using in vitro and in silico studies

LOURDES SCIU; M DANIELA SANTI; JORGE CANTERO; PABLO COLOMER; MARGOT PAULINO ZUNINI; GABRIELA ORTEGA (CORRESPONDING AUTHOR JUNTO A LAURA MOYANO); LAURA MOYANO

SN Applied Sciences

Springer

Año: 2020 vol. 2

eterocyclic 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 activity with IC50 values range of 0.9?2.9 μM. While the inhibition performance of pyrazolotriazinones was not more active than reference inhibitor allopurinol (IC50 = 0.247 ± 0.004) μM, these nuclei provide a platform for new and more potent XO inhibitors. Accordingly, molecular modeling methods were carried out to understand the compounds-enzyme binding mode. First, we have performed a qualitative SAR study using the MOE? SAR tool. This study showed three common scaffolds and the most active was identified. These results are certainly valuable and will be taken into account in future synthesis of structurally related compou