The modern approaches of analysis of dihydroquercetin stereoisomeric composition

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Dihydroquercetin (DHQ) is a representative of the flavonoid family. This natural polyphenol is known for its high ability to bind active oxygen species, which is used to explain its wide range of biological activities. However, the fact that DHQ has two chiral centers in the positions 2 and 3 of the pyranone ring is often ignored. By the way, such structure allowing this compound to exist in four stereoisomers. The current literature review was prepared to systemize the information for the analysis of DHQ stereoisomers to control the quality of future chiral remedies. During the study, it was found that relying on polarimetry results for research and the development of regulatory documentation is difficult due to the heterogeneity of data on the optical activity of flavanonol molecules. Information on the NMR spectroscopy of DHQ diastereomers is more reliable, but this method does not allow for the identification of individual stereoisomers and is not implemented in routine pharmaceutical analysis. Among all the methods considered, only HPLC is currently characterized by sufficient enantioselectivity. The results of the literature review indicate that chromatography is the most promising method for quality control of chiral pharmaceuticals, which can be developed based on DHQ. Referring to the history of pharmaceutical science, it seems unnecessary to remind the important role of the stereochemical composition of active pharmaceutical ingredient in ensuring the efficacy and safety of drugs. The results of our review are intended to draw the attention of the scientific community to significant gaps in the current system of knowledge and regulatory documentation.

Full Text

Restricted Access

About the authors

Roman P. Terekhov

FSAEI of HE I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Author for correspondence.
Email: terekhov_r_p@staff.sechenov.ru
ORCID iD: 0000-0001-9206-8632

PhD in pharmaceutical sciences, associate professor at the Department of Chemistry of Nelyubin Institute of Pharmacy

Russian Federation, Trubetskaya str., 8/2, Mosсow, 119991

Anastasiya D. Savina

FSAEI of HE I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: savina_a_d@student.sechenov.ru
ORCID iD: 0009-0000-5123-8746

student at Nelyubin Institute of Pharmacy

Russian Federation, Trubetskaya str., 8/2, Mosсow, 119991

Denis I. Pankov

FSAEI of HE I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: pankov_d_i@staff.sechenov.ru
ORCID iD: 0009-0007-6195-6400

assistant professor at the Department of Chemistry of Nelyubin Institute of Pharmacy

Russian Federation, Trubetskaya str., 8/2, Mosсow, 119991

Ilya D. Nikitin

FSAEI of HE I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: nikitin_i_d@student.sechenov.ru
ORCID iD: 0000-0001-8044-0548

student at Nelyubin Institute of Pharmacy

Russian Federation, Trubetskaya str., 8/2, Mosсow, 119991

Irina A. Selivanova

FSAEI of HE I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: selivanova_i_a@staff.sechenov.ru
ORCID iD: 0000-0002-2244-445X

ScD in pharmaceutical sciences, professor, professor at the Department of Chemistry of Nelyubin Institute of Pharmacy

Russian Federation, Trubetskaya str., 8/2, Mosсow, 119991

References

  1. Aware C.B., Patil D.N., Suryawanshi S.S. et al. Natural bioactive products as promising therapeutics: A review of natural product-based drug development. Journal of South African botany. 2022; 151: 512–28. doi: 10.1016/j.sajb.2022.05.028
  2. Terekhov R.P., Melnikov E.S., Nikitin I.D. et al. Diastereomers of Spheroidal Form and Commercially Available Taxifolin Samples. Scientia Pharmaceutica. 2024; 92 (1): 5. doi: 10.3390/scipharm92010005
  3. Gaggeri R., Rossi D., Christodoulou M. et al. Chiral Flavanones from Amygdalus lycioides Spach: Structural Elucidation and Identification of TNF alpha Inhibitors by Bioactivity-guided Fractionation. Molecules. 2012; 17 (2): 1665–74. doi: 10.3390/molecules17021665
  4. Lundgren L.N., Theander O. Cis- and trans-dihydroquercetin glucosides from needles of Pinus sylvestris. Phytochemistry. 1988; 27 (3): 829–32. doi: 10.1016/0031-9422(88)84101-3
  5. Yoon K.D., Lee J.Y., Kim T.Y. et al. In Vitro and in Vivo Anti-Hyperglycemic Activities of Taxifolin and Its Derivatives Isolated from Pigmented Rice (Oryzae sativa L. cv. Superhongmi). J. Agric. Food Chem. 2020; 68 (3): 742–50. doi: 10.1021/acs.jafc.9b04962
  6. Sato M., Murakami K., Uno M. et al. Structure–Activity Relationship for (+)-Taxifolin Isolated from Silymarin as an Inhibitor of Amyloid β Aggregation. Biosci. Biotechnol. Biochem. 2013; 77 (5): 1100–3. doi: 10.1271/bbb.120925
  7. Imai T., Inoue S., Ohdaira N. et al. Heartwood extractives from the Amazonian trees Dipteryx odorata, Hymenaea courbaril, Astronium lecointei and their antioxidant activities. Journal of Wood Science. 2008; 54 (6): 470–75. doi: 10.1007/s10086-008-0975-3
  8. Lee E.H., Kim H.J., Song Y.S. et al. Constituents of the stems and fruits of Opuntia ficus-indica var. saboten. Arch. Pharm. Res. 2003; 26 (12): 1018–23. doi: 10.1007/BF02994752
  9. Inada A., Murata H., Somekawa M. et al. Phytochemical Studies of Seeds of Medicinal Plants. II. A New Dihydroflavonol Glycoside and a New 3-Methyl-1-butanol Glycoside from Seeds of Platycodon grandiflorum A. DE CANDOLLE. Chem. Pharm. Bull. (Tokyo). 1992; 40 (11): 3081–3. doi: 10.1248/CPB.40.3081
  10. Kuroyanagi M., Yamamoto Y., Fukushima S. et al. Chemical studies on the constituents of Polygonum nodosum. Chem. Pharm. Bull. (Tokyo). 1982; 30 (5): 1602–8. doi: 10.1248/CPB.30.1602
  11. Kiehlmann E., Li E.P.M. Isomerization of Dihydroquercetin. J. Nat. Prod. 1995; 58 (3): 450–5. doi: 10.1021/np50117a018
  12. Kasai R., Hirono S., Chou W.H. et al. Sweet dihydroflavonol rhamnoside from leaves of Engelhardtia chrysolepis, a chinese folk medicine, hung-qi. Chem. Pharm. Bull. (Tokyo). 1988; 36 (10): 4167–70. doi: 10.1248/CPB.36.4167
  13. Sakurai A., Okumura Y. Chemical Studies on the Mistletoe. V. The Structure of Taxillusin, a New Flavonoid Glycoside Isolated from Taxillus kaempferi. Bull. Chem. Soc. Jpn. 1983; 56 (2): 542–4. doi: 10.1246/bcsj.56.542
  14. Nonaka G.-I., Goto Y., Kinjo J.-E. et al. Tannins and related compounds. LII Studies on the constituents of the leaves of Thujopsis dolabrata SIEB. et ZUCC. // Chem. Pharm. Bull. (Tokyo). 1987; 35 (3): 1105–8. doi: 10.1248/cpb.35.1105
  15. Ohmura W., Ohara S., Hashida K. et al. Hydrothermolysis of Flavonoids in Relation to Steaming of Japanese Larch Wood. Holzforschung. 2002; 56 (5): 493–7. doi: 10.1515/HF.2002.076
  16. Yoshida T., Zhe X.J., Okuda T. Taxifolin apioside and davuriciin M1, a hydrolysable tannin from Rosa davurica. Phytochemistry. 1989; 28 (8): 2177–81. doi: 10.1016/S0031-9422(00)97939-1
  17. Mohammed H.A., Almahmoud S.A., El-Ghaly E.M. et al. Comparative Anticancer Potentials of Taxifolin and Quercetin Methylated Derivatives against HCT-116 Cell Lines: Effects of O -Methylation on Taxifolin and Quercetin as Preliminary Natural Leads. ACS Omega. 2022; 7 (50): 46629–39. doi: 10.1021/acsomega.2c05565
  18. Braune A., Gütschow M., Engst W., Blaut M. Degradation of Quercetin and Luteolin by Eubacterium ramulus. Appl. Environ. Microbiol. 2001; 67 (12): 5558–67. doi: 10.1128/AEM.67.12.5558-5567.2001
  19. Trofimova N.N., Stolpovskaya E.V., Babkin V.A. et al. The structure and electrochemical properties of metal complexes with dihydroquercetin. Russian J. of Bioorganic Chemistry. 2015; 41 (7): 745–52. doi: 10.1134/S1068162015070146
  20. Kuspradini H., Mitsunaga T., Ohashi H. Antimicrobial activity against Streptococcus sobrinus and glucosyltransferase inhibitory activity of taxifolin and some flavanonol rhamnosides from kempas (Koompassia malaccensis) extracts. J. of Wood Science. 2009; 55 (4): 308–13. doi: 10.1007/s10086-009-1026-4
  21. Baderschneider B., Winterhalter P. Isolation and Characterization of Novel Benzoates, Cinnamates, Flavonoids, and Lignans from Riesling Wine and Screening for Antioxidant Activity. J. Agric. Food Chem. 2001; 49 (6): 2788–98. doi: 10.1021/jf010396d
  22. Turnbull J.J., Nakajima J., Welford R.W. et al. Mechanistic Studies on Three 2-Oxoglutarate-dependent Oxygenases of Flavonoid Biosynthesis. J. Biol. Chem. 2004; 279 (2): 1206–16. doi: 10.1074/jbc.M309228200
  23. Jiang W.-J., Ishiuchi K., Furukawa M. et al. Stereospecific inhibition of nitric oxide production in macrophage cells by flavanonols: Synthesis and the structure–activity relationship. Bioorg. Med. Chem. 2015; 23 (21): 6922–9. doi: 10.1016/j.bmc.2015.09.042
  24. Fedorova T.E., Fedorov S.V., Babkin V.A. Phenolic Compounds of Picea obovata Ledeb. Bark. Russian Journal of Bioorganic Chemistry. 2019; 45 (7): 927–32. doi: 10.1134/S1068162019070045
  25. Nifant’ev E.E., Koroteev M.P., Kaziev G.Z. et al. On the problem of identification of the dihydroquercetin flavonoid. Russian J. of general chemistry. 2006; 76 (1): 161–3. doi: 10.1134/S1070363206010324
  26. Wang X., Zhou H., Zeng S. Identification and assay of 3'-O-methyltaxifolin by UPLC–MS in rat plasma. J. Chromatogr. B. 2012; 911: 34–42. doi: 10.1016/j.jchromb.2012.09.006
  27. Elsinghorst P.W., Cavlar T., Müller A. et al. The Thermal and Enzymatic Taxifolin–Alphitonin Rearrangement. Journal of Natural Products. 2011; 74 (10): 2243–9. doi: 10.1021/np200639s
  28. Vega-Villa K.R., Remsberg C.M., Ohgami Y. et al. Stereospecific high-performance liquid chromatography of taxifolin, applications in pharmacokinetics, and determination in tu fu ling (Rhizoma smilacis glabrae) and apple (Malus × domestica). Biomed. Chromatogr. 2009; 23 (6): 638–46. doi: 10.1002/bmc.1165

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Stereoisomers of dihydroquercetin: а – 2R,3R-configuration, б – 2R,3S-configuration, в – 2S,3R-configuration, г – 2S,3S-configuration

Download (23KB)
Indexing metadata
3. Fig. 2. Funnel plot of relationship between concentration of DHQ in methanol solution and specific rotation value (p=0,01)

Download (12KB)
Indexing metadata

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies