Study on the Interaction between Apigenin and Various Phenolic Acids in Xanthine Oxidase Inhibition Using Molecular Docking

Liow, Khai Li (2022) Study on the Interaction between Apigenin and Various Phenolic Acids in Xanthine Oxidase Inhibition Using Molecular Docking. Final Year Project (Bachelor), Tunku Abdul Rahman University College.

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Abstract

Gout is a form of inflammatory arthritis as a result of high serum uric acid. The formation of uric acid is catalyzed by the enzyme xanthine oxidase (XO). XO is a homodimer with each subunit composed of a molybdopterin cofactor that is responsible for the oxidation of xanthine to uric acid. By inhibiting the activity of XO, the concentration of uric acid in the serum can be reduced, thus aiding the treatment of gout. Examples of XO inhibitors include allopurinol, a competitive inhibitor. However, its usage is limited due to its adverse effects such as hypersensitivity syndrome, renal toxicity, and liver impairment. For this reason, the search for a new substitute for allopurinol is demanded. In this study, in silico studies were conducted to investigate the interaction between apigenin and 24 phenolic acids ((+)-chebulic acid, caffeic acid, caftaric acid, chlorogenic acid, chicoric acid, cinnamic acid, cis-p-coumaric acid, cis-sinapic acid, coutaric acid, eudesmic acid, fertaric acid, ferulic acid, gallic acid, gentisic acid, m-coumaric acid, m-hydroxybenzoic acid, phloroglucinol carboxylic acid, p-hydroxybenzoic acid, protocatechuic acid, salicylic acid, sinapic acid, syringic acid, trans-cinnamic acid, vanillic acid). In vitro studies were further conducted to investigate the inhibition of XO by using a combination of apigenin and trans-cinnamic acid in different ratios. In silico studies showed the interaction between apigenin and four phenolic acids (coutaric acid, cinnamic acid, chlorogenic acid, chicoric acid, and (+)-chebulic acid) had a lower binding affinity towards XO compared to other phenolic acids. Their best docking score were -3.8 kcal mol-1 (apigenin – coutaric acid) and -4.4 kcal mol-1 (coutaric acid – apigenin); -2.7 kcal mol-1 (apigenin – cinnamic acid) and -4.4 kcal mol-1 (cinnamic acid – apigenin); -3.5 kcal mol-1 (apigenin – chlorogenic acid) and -4.2 kcal mol-1 (chlorogenic acid – apigenin); -2.3 kcal mol-1 (apigenin – chicoric acid) and -4.1 kcal mol-1 (chicoric acid – apigenin); -3.6 kcal mol-1 (apigenin – (+)-chebulic acid) and -4.0 kcal mol-1 ((+)-chebulic acid – apigenin). Further in vitro studies on XO inhibitory activity and were continued. Based on the XO inhibitory activity in this study, apigenin showed 22.66 ± 2.46% of XOI%, and trans-cinnamic acid showed 25.59 ± 0.72% of XOI%. XO inhibitory assay between apigenin and trans-cinnamic acid in 1:1 ratio had the highest XOI% of 43.21 ± 2.75 %