Antioxidant activity and in vitro and in silico gout inhibitory effect of benzylideneacetophenone derivatives

Chalcones were experimentally investigated for their ability to act as antioxidants and as xanthine oxidase inhibitors in vitro and in silico. The antioxidant ability of chalcone (benzylideneacetophenone, A) and 7 chalcone derivatives (1-phenyl-3(benzodioxolyl)-2-propen-1-one, B; 4’-nitro-4-dimethylaminochalcone, C; 4-nitro-4-methoxychalcone, D; 1(4’-nitrophenyl)-3(1,3-benzodioxolyl)-2-propen-1-one, E; 1-phenyl-3(γ-benzopyranoyl)-2-propen-1-one, F; 1-(4’-nitrophenyl)-3(γ-benzopyranoyl)-2-propen-1-one, G; 4-dimethylaminochalcone, H) was evaluated spectrophotometrically utilizing three methods: DPPH, copper chelation, and hydrogen peroxide scavenging. Also in vitro xanthine oxidase inhibitory activity and molecular docking using computer simulation were carried out. In the DPPH radical scavenging, samples A, B and G showed higher percentages of inhibiting DPPH as compared to the standard antioxidant gallic acid. The copper chelating ability of the compounds indicated that samples A, C, and F chelate copper efficiently than EDTA. The percent of hydrogen peroxide scavenging by chalcones indicated that samples C, D, G, and H are better antioxidants. Also, the in vitro xanthine oxidase inhibitory activity of chalcones showed that samples inhibited the enzyme but not as high as the reference drug allopurinol. The molecular docking studies revealed that samples C, E, F, and G had higher docking scores of -7.98, -8.51, -8.67 and -10.07, which were higher than -7.59 kcal/mol for allopurinol. Therefore, samples C, E, F, and G showed antioxidant and in vitro xanthine oxidase inhibition as well as better docking values. These results made these chalcones promising targets against xanthine oxidase or gout.