Synthesis and xanthine oxidase inhibitory activity of 5,6-dihydropyrazolo/pyrazolo[1,5-c]quinazoline derivatives

• 5,6-Dihydropyrazolo/pyrazolo[1,5-c]quinazolines were designed and synthesized.
• They inhibited xanthine oxidase in in vitro.
• Some notions about structure activity relationships are presented.
• Compound 6g inhibited xanthine oxidase and scavenged free radical effectively.
• Binding mode of 6g into xanthine oxidase through in silico studies is discussed.

Some 5,6-dihydropyrazolo/pyrazolo[1,5-c]quinazoline derivatives were rationally designed, synthesized and evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Some notions about structure activity relationships are presented. The compounds 6g, 6h and 6e were found to be significantly active against XO. The compound 6g emerged as the most potent XO inhibitor as compared to allopurinol and free radical scavenger. The molecular docking of 6g into the XO active site highlighted its mode of binding and important interactions such as hydrogen bonding, π–π stacking with amino acid residues like Ser876, Thr1010, Phen914, Phe1009 and Phe649 and its close proximity to dioxothiomolybdenum (MOS).

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