Synthesis, enzyme inhibition and molecular docking studies of pyrazolo [1,5-a][1,3,5] triazine derivatives as potential antioxidant agents

We developed and produced a series of pyrazolo[1,5-a][1,3,5]triazine derivatives (5a-l) in three stages using condensation, intramolecular ring annulation, and acylation processes under moderate conditions. Various spectroscopic techniques and elemental analyses were used to characterize all newly synthesized molecules. By using FRAP and DPPH radical scavenging assays, the antioxidant activity of these compounds was assessed. These conjugates were shown to have moderate to substantial antioxidant activity in both assays. In DPPH and FRAP experiments, compounds 5c, 5d, 5f, and 5 g had the highest levels of antioxidants, with IC50 values of 80.33-99.04 & mu;M and 85.69-102.81 & mu;M, respectively. The SAR study's findings indicate that compounds with electron-donating groups (5b-g) are more potent than those with electron-withdrawing groups (5h-l) and unsubstituted compound (5a). Additionally, the lipoxygenase (LOX) and xanthine oxidase (XO) enzymes were used to assess the potent compounds (5b-g) for their ability to suppress enzyme activity. With an IC50 value of 16.85-49.02 & mu;M and 23.01-57.38 & mu;M, respectively, these compounds significantly inhibited the activity of the LOX and XO enzymes. Particularly, a number of the designed compounds bearing hydroxyl substituted on phenyl ring linked to pyrazolo[1,5-a][1,3,5]triazine system showed excellent not only in antioxidant activity but also in LOX and XO enzyme inhibition. Among these compound 5f was proved to be the top one with an antioxidant and enzyme inhibition ability that was even comparable to that of the standards used. Finally, molecular docking studies of the most effective compounds have been carried out, and the results have shown that the docking scores obtained for compounds 5c, 5f, and 5 g have a significant correlation with the values of antioxidant and enzyme inhibition activity that were found through experimentation.

Automated summary

We developed a series of pyrazolo[1,5-a][1,3,5]triazine derivatives (5a-l) through condensation, intramolecular ring annulation, and acylation processes. These compounds exhibited moderate to substantial antioxidant activity and were effective in inhibiting LOX and XO enzyme activity. Particularly, compound 5f showed excellent antioxidant and enzyme inhibition abilities. Molecular docking studies further confirmed the correlation between docking scores and experimental antioxidant and enzyme inhibition activity.