title: Design, synthesis and evaluation of 2,4-diarylpyrano[3,2-c]chromen-5(4H)-one as a new class of non-purine xanthine oxidase inhibitors.
abstract: Abstract Keeping in view the recent success of molecular hybridization technique in drug design, 2,4-diarylpyrano[3,2-c]chromen-5(4H)-ones as conjugates of coumarins and chalcones have been designed and synthesized in the present study. The catalytic efficiency of various Lewis acids for the synthesis of designed conjugates under neat conditions was investigated, and SiO2(200-400 mesh)-ZnCl2was optimized as the best catalyst among the tested ones. The conjugates were evaluated for in-vitro xanthine oxidase activity. The results of the in-vitro assay were quite promising as some conjugates were endowed with remarkable inhibitory potential against the enzyme. HV-8, 11 and 12 were found to be high-potent inhibitors with HV-11 (the most potent inhibitor) possessing an IC50value of 2.21 µM. The most active conjugate HV-11 was evaluated for the type of inhibition and was found to be a mixed type inhibitor. The compliance of some selected conjugates to the Lipinski rule was also calculated.
authors.affiliation: Department of Pharmaceutical sciences, Guru Nanak Dev University , Amritsar, Punjab , India and.
authors.forename: Harpreet S
authors.initials: HS
authors.lastname: Virdi
authors.forename: Sahil
authors.initials: S
authors.lastname: Sharma
authors.forename: Samir
authors.initials: S
authors.lastname: Mehndiratta
authors.forename: P M S
authors.initials: PM
authors.lastname: Bedi
authors.forename: Kunal
authors.initials: K
authors.lastname: Nepali
keywords: Conjugates; inhibition; lipinski rule; mixed; silica; xanthine oxidase