Validation of in Silico Docking Analysis of Oligophenylpropanoids to Xanthine Oxidase by Correlation with in Vitro Bioassay and Its Application to Phlorotannins
Journal of Drug Design and Medicinal Chemistry
Volume 6, Issue 1, March 2020, Pages: 1-6
Received: Feb. 12, 2020; Accepted: Mar. 13, 2020; Published: Mar. 31, 2020
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Sheau Ling Ho, Department of Chemical & Materials Engineering, Chinese Culture University, Taipei, Taiwan, ROC
Sheng-Fa Tsai, School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC
Ching-Ting Lin, School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC
Hyeung-Rak Kim, Departments of Food and Nutrition, Pukyong National University, Busan, Korea
Shoei-Sheng Lee, School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC
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The oligo-phenylpropanoids 1−7, isolated from Hyptis rhombodes, have been found to possess potent inhibitory activity against xanthine oxidase (EC, bovine milk). To rationalize such activity, computer assisted docking of these compounds and allopurinol, a positive control, on the xanthine oxidase was undertaken in this study. The docking scores, obtained by London (trimatch)−refinement (Forcefield Affinity ΔG) mode, showed good correlation with the IC50 values. That the compounds possessing 7′-Z configuration had much better inhibitory activity than those 7′-E isomers is well rationalized by this docking study. Virtual screening of eight phlorotannins (8−15) by this refinement mode found good docking scores. The bioassay result of three available ones (9, 12, 13) also indicated the consistency with the docking scores. While refined by Forcefield−London mode, certain inconsistency among the docking score and bioassay result was observed on either phenylpropanoid oligomers or three phlorotannins. Hence the London (trimatch)−refinement (Forcefield−Affinity ΔG) mode is recommended for virtual screening of the related phenolics. Three phlorotannins (11, 14, 15) were found to have better docking score than 6,6'-bieckol (12) and dieckol (13), both showing comparable inhibitory activity against xanthine oxidase to allopurinol, and thus they deserve further study. In addition, as these phlorotannins are rich in the Ecklonia genus, the common edible seaweeds such as E. cava and E. stolonifera are demonstrated to be beneficial to hyperuricemic patients.
Xanthine Oxidase Inhibitors, Oligo-phenylpropanoids, Bioassay, Molecular Docking, Phlorotannins
To cite this article
Sheau Ling Ho, Sheng-Fa Tsai, Ching-Ting Lin, Hyeung-Rak Kim, Shoei-Sheng Lee, Validation of in Silico Docking Analysis of Oligophenylpropanoids to Xanthine Oxidase by Correlation with in Vitro Bioassay and Its Application to Phlorotannins, Journal of Drug Design and Medicinal Chemistry. Vol. 6, No. 1, 2020, pp. 1-6. doi: 10.11648/j.jddmc.20200601.11
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R. Hille (2006) Structure and function of xanthine oxidoreductase. European Journal of Inorganic Chemistry 10: 1913−1926.
Rock, K. L., H. Kataoka, J. J. Lai (2013) Uric acid as a danger signal in gout and its comorbidities. Nature Reviews Rheumatology 9: 13−23.
Pacher, P., A. Nivorozhkin, C. Szabo (2006) Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacology Review 58: 87−114.
Robinson, P. C., N. Dalbeth (2015) Advances in pharmacotherapy for the treatment of gout. Expert Opinion on Pharmacotherapy 16: 533−546.
Tsai, S. F., S. S. Lee (2014) Neolignans as xanthine oxidase inhibitors from Hyptis rhomboids. Phytochemistry 101: 121–127.
Enroth, C., B. T. Eger, K. Okamoto, T. Nishino, T. Nishino, E. F. Pai (2000) Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion. Proceedings of the National Academy of Sciences USA 97: 10723−10728.
Molecular Operating Environment (MOE) 2010.10. (2010). Chemical Computing Group, Inc; Montreal, Quebec.
Herbert Edelsbrunner, Ernst P. Mücke (1992) Three-dimensional alpha shapes. Mathematics, Computer Science VVS: 75−82.
Matteo Aldeghi, Alexander Heifetz, Michael J. Bodkin, Stefan Knapp and Philip C. Biggin (2016) Accurate calculation of the absolute free energy of binding for drug molecules. Chemical Science 7: 207−218.
María J. R. Yunta (2016) Docking and Ligand Binding Affinity: Uses and Pitfalls. American Journal of Modeling and Optimization 4 (3): 74-114.
T. A. Halgren (1996) Merck molecular force field. 1. Basis, form, scope, parameterization, and performance of MMFF94. Journal of Computational Chemistry 17: 490−519.
Clark AM, Labute P. (2007) 2D depiction of protein-ligand complexes. J Chem Inf Model. 47 (5): 1933–1944.
Hsu, F. C., S. F. Tsai, S. S. Lee (2019) Chemical investigation of Hyptis suaveolens seed, a potential antihyperuricemic nutraceutical, with assistance of HPLC-SPE-NMR. Journal of Food and Drug Analysis 27: 897−905 and reference cited therein.
Lee, M. S., T. Shin, T. Utsuki, J. S. Choi, D. S. Byun, H. Kim (2012) Isolation and identification of phlorotannins from Ecklonia stolonifera with antioxidant and hepatoprotective properties in tacrine-treated HepG2 cells. Journal of Agriculture and Food Chemistry 60: 5340−5349.
Lee, J. H., J. Y. Ko, J. Y. Oh, C. Y. Kim, H. J. Lee, J. Kim, Y. J. Jeon (2014) Preparative isolation and purification of phlorotannins from Ecklonia cava using centrifugal partition chromatography by one-step. Food Chemistry 158: 433−437.
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