Molecular modeling of the interaction of the dihydroquercetin and its metabolites with cyclooxygenase-2
https://doi.org/10.20538/1682-0363-2019-3-101-106
Abstract
Background. Dihydroquercetin (DHQ) is a natural flavonoid. It has a wide range of pharmacological effects, which includes anti-inflammatory activity. There is a gap in our knowledge about the biochemical mechanisms of the therapeutic potency implementation of this compound. This fact slows down the process of the drug development using DHQ. Molecular modeling is designed to further translate the research from the fundamental experimentation to the real clinical practice. Purpose. The study objective was to estimate DHQ as a cyclooxygenase-2 (COX-2) inhibitor by using in silico analysis.
Materials and methods. The information about the COX-2 structure was obtained from the Protein Data Bank (code 5KIR). The 3D-models of DHQ were generated by using the ChemBioDraw Ultra software. Docking was carried out in the GOLD program after the corresponding validation of molecular modeling algorithms based on experimental data of X-ray diffraction analysis.
Results. The design of this study is based on the rational selecting of the virtual ligand structures. It gives an opportunity to optimize the quantum-mechanical calculation. By using in silico analysis, it was shown that DHQ and some of its metabolites demonstrate ability of binding to SER353, SER530, and ARG513 of COX-2 at the catalytic site.
Conclusion. Important α-amino acids for intermolecular interaction of DHQ and its metabolites with COX-2 were determined during this study. Our data can be used for the development of new antiinflammatory drugs on the base of DHQ.
About the Authors
R. P. Terekhov
Sechenov University;
Fraunhofer Institute for Cell Therapy and Immunology
Russian Federation
Russian Federation
Student, Institute of Pharmacy, 8/2 Bolshaya Pirogovskaya Str., Moscow, 119991;
1 Perlickstraße, Leipzig, 04103
I. A. Selivanova
Sechenov University
Russian Federation
Russian Federation
DPhSc, Professor, Department of Chemistry, Institute of Pharmacy,
8/2 Bolshaya Pirogovskaya Str., Moscow, 119991
References
1. Zhuravleva M.V., Kukes V.G., Prokofiev A.B., Serebrova S.Yu., Gorodeckaya G.I., Berdnikova N.G. Rational Use of NSAIDs – Balance of Efficiency and Safety (Review). International Journal of Applied and Basic Research. 2016; 6 (4): 687–696 (in Russ.).
2. Dremova N.B., Solomka S.V. Sociological research of the relation of modern patients to the appointed pharmacotherapy. In book: “Effetive сlinical practice: challenges and opportunities for a modern doctor”; N.K. Gorshunova, editor. Kursk: Kursk State Medical University Publ., 2017: 189–202 (in Russ.).
3. Terekhov R.P., Selivanova I.A., Tyukavkina N.A., Fenin A.A. Analysis of dihydroquercetin amorphous form by chromato-mass-spectrometry: works of the conference “Medical plants of the botanic garden”, 2016 Sept. 21–22, Moscow, Russia. Moscow: Sechenov First Moscow State Medical University Publ., 2016: 131 (in Russ.).
4. Plotnikov M.B., Tyukavkina N.A., Plotnikova T.M. Medicaments on the base of Dikvetin. Tomsk: Tomsk University Publ., 2005: 228 (in Russ.).
5. Raj U., Varadwaj P.K. Flavonoids as multi-target inhibitors for proteins associated with Ebola virus: in silico discovery using virtual screening and molecular docking studies. Interdisciplinary Sciences Computational Life Sciences. 2016; 8 (2): 132–141. DOI: 10.1007/s12539-015-0109-8.
6. Verma Sh., Singh A., Mishra A. Taxifolin acts as type I inhibitor for VEGFR-2 kinase: Stability evaluation by molecular dynamic simulation. Journal of Applied Pharmaceutical Science. 2012; 2 (1): 41–46.
7. Yang P., Xu F., Li H.F., Wang Y., Li F.C., Schang M.Y., Liu G.X., Wang X., Cail S.Q. Detection of 191 taxifolin metabolites and their distribution in rats using HPLC-ESI-IT-TOF-MS(n). Molecules. 2016; 21 (9): 1209–1234. DOI: 10.3390/molecules21091209.
8. Ostrikova O.I. Computer simulation of glicophorin A and 4-methyl-2.6-diisobornilfenol interaction by autodock and hexserver programs. Bulletin of Siberian Medicine. 2014; 13 (5): 62–66 (in Russ.).
9. Holtje H.-D., Zippl V., Ronyan D., Volkers G. Molecular modeling: theory and practice. Moscow: BINOM Publ., 2015: 319 (in Russ.).
10. Orlando B.J., Malkowski M.G. Crystal structure of rofecoxib bound to human cyclooxygenase-2. Acta Crystallographica F. Struct Biol Commun. 2016; 72 (10): 772–776. DOI: 10.1107/S2053230X16014230.
Review
For citations:
Terekhov R.P., Selivanova I.A. Molecular modeling of the interaction of the dihydroquercetin and its metabolites with cyclooxygenase-2. Bulletin of Siberian Medicine. 2019;18(3):101-106. (In Russ.) https://doi.org/10.20538/1682-0363-2019-3-101-106
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