4,6-Diaryl/heteroarylpyrimidin-2(1H)-ones as a new class of xanthine oxidase inhibitors.
A series of 4,6-diaryl/heteroarylpyrimidones was synthesized employing silica-supported fluoroboric acid under solvent-free conditions in a microwave reactor. The catalytic influence of HBF4-SiO2 was investigated in detail to optimize the reaction conditions. The synthesized compounds were evaluated for in vitro xanthine oxidase (XO) inhibitory activity for the first time. Structure-activity relationship analyses are also presented. Among the synthesized compounds, VA-5, -9, -10, -12, -22, -23, and -25 were the active inhibitors with IC50 values ranging from 6.45 to 13.46 µM. Compound VA-25 with a pyridinyl ring as ring A and a thiophenyl ring as ring B emerged as the most potent XO inhibitor (IC50 = 6.45 µM) in comparison to allopurinol (IC50 = 12.24 µM). Some of the important interactions of VA-25 with the amino acid residues of the active site of XO were figured out by molecular modeling studies.
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.
Shiwani
S
Shukla
Dinesh
D
Kumar
Ritu
R
Ojha
Manish K
MK
Gupta
Kunal
K
Nepali
Preet M S
PM
Bedi
D000818:Animals; D001881:Borates / Q000737:chemistry; D002384:Catalysis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008872:Microwaves; D008892:Milk / Q000201:enzymology; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012822:Silicon Dioxide / Q000737:chemistry; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
D001881:Borates; D004791:Enzyme Inhibitors; D011744:Pyrimidinones; D012822:Silicon Dioxide; D014969:Xanthine Oxidase; C098759:fluoroboric acid
Catalyst; Fluoroboric acid; Inhibitors; Microwave radiation; Pyrimidones; Silica; Xanthine oxidase