Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
December-2017 Volume 16 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2017 Volume 16 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Synthesis of regioselectively acylated quercetin analogues with improved antiplatelet activity

  • Authors:
    • Yu Duan
    • Na Sun
    • Min Xue
    • Xiaolan Wang
    • Hu Yang
  • View Affiliations / Copyright

    Affiliations: School of Pharmacy, Weifang Medical College, Weifang, Shandong 261053, P.R. China, Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, VA 23119, USA
  • Pages: 9735-9740
    |
    Published online on: October 12, 2017
       https://doi.org/10.3892/mmr.2017.7781
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The aim of the present study was to report on a complete synthetic approach, namely benzylation-hydrolysis-acylation‑hydrogenation, to the synthesis of regioselectively acylated quercetin analogues using low‑cost rutin as a starting material. Three quercetin analogues, quercetin‑3‑O‑propionate (Q‑pr), quercetin‑3‑O‑butyrate (Q‑bu) and quercetin‑3‑O‑valerate (Q‑va), containing 3‑, 4‑ and 5‑carbon aliphatic acyl chains, respectively, were synthesized and characterized with 1H nuclear magnetic resonance (NMR), 13C NMR and mass spectrometry. Compared with quercetin, all three analogues exhibited improved lipophilicity. The lipophilicity of the analogue increased with increasing acyl chain length. Q‑va exhibited the highest lipophilicity among the three analogues, but a lower water solubility compared with quercetin. By contrast, Q‑pr and Q‑bu exhibited 8.2‑ and 4.7‑fold higher water solubility compared with quercetin, respectively. The in vitro and in vivo studies demonstrated that Q‑pr and Q‑bu were more effective whereas Q‑va was less effective in inhibiting platelet aggregation compared with quercetin. These results indicated that the water solubility and the lipophilicity of the analogues must be improved in order to achieve higher antiplatelet activity, and an optimal acyl chain length is crucial for the synthesized quercetin analogues to be more effective.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Hertog MG, Hollman PC, Katan MB and Kromhout D: Intake of potentially anticarcinogenic flavonoids and their determinants in adults in the Netherlands. Nutr Cancer. 20:21–29. 1993. View Article : Google Scholar : PubMed/NCBI

2 

Chen Y and Deuster P: Comparison of quercetin and dihydroquercetin: Antioxidant-independent actions on erythrocyte and platelet membrane. Chem Biol Interact. 182:7–12. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Fuentes E and Palomo I: Relationship between Platelet PPARs, cAMP levels, and P-Selectin expression: Antiplatelet activity of natural products. Evid Based Complement Alternat Med. 2013:8617862013. View Article : Google Scholar : PubMed/NCBI

4 

Fuentes E and Palomo I: Antiplatelet effects of natural bioactive compounds by multiple targets: Food and drug interactions. J Funct Foods. 6:73–81. 2014. View Article : Google Scholar

5 

Mosawy S, Jackson DE, Woodman OL and Linden MD: Treatment with quercetin and 3′,4′-dihydroxyflavonol inhibits platelet function and reduces thrombus formation in vivo. J Thromb Thrombolys. 36:50–57. 2013. View Article : Google Scholar

6 

Navarro-Núñez L, Lozano ML, Martínez C, Vicente V and Rivera J: Effect of quercetin on platelet spreading on collagen and fibrinogen and on multiple platelet kinases. Fitoterapia. 81:75–80. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Navarro-Núñez L, Rivera J, Guerrero JA, Martínez C, Vicente V and Lozano ML: Differential effects of quercetin, apigenin and genistein on signalling pathways of protease-activated receptors PAR(1) and PAR(4) in platelets. Brit J Pharmacol. 158:1548–1556. 2009. View Article : Google Scholar

8 

Oh WJ, Endale M, Park SC, Cho JY and Rhee MH: Dual roles of quercetin in platelets: Phosphoinositide-3-kinase and MAP kinases inhibition, and cAMP-dependent vasodilator-stimulated phosphoprotein stimulation. Evid Based Complement Alternat Med. 2012:4852622012. View Article : Google Scholar : PubMed/NCBI

9 

Ferry DR, Smith A, Malkhandi J, Fyfe DW, deTakats PG, Anderson D, Baker J and Kerr DJ: Phase I clinical trial of the flavonoid quercetin: Pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin Cancer Res. 2:659–668. 1996.PubMed/NCBI

10 

Leonarduzzi G, Testa G, Sottero B, Gamba P and Poli G: Design and development of nanovehicle-based delivery systems for preventive or therapeutic supplementation with flavonoids. Curr Med Chem. 17:74–95. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Justino GC, Santos MR, Canário S, Borges C, Florêncio MH and Mira L: Plasma quercetin metabolites: Structure-antioxidant activity relationships. Arch Biochem Biophys. 432:109–121. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Wang H and Joseph JA: Structure-activity relationships of quercetin in antagonizing hydrogen peroxide-induced calcium dysregulation in PC12 cells. Free Radic Biol Med. 27:683–694. 1999. View Article : Google Scholar : PubMed/NCBI

13 

Montenegro L, Carbone C, Maniscalco C, Lambusta D, Nicolosi G, Ventura CA and Puglisi G: In vitro evaluation of quercetin-3-O-acyl esters as topical prodrugs. Int J Pharm. 336:257–262. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Saija A, Tomaino A, Trombetta D, Pellegrino ML, Tita B, Messina C, Bonina FP, Rocco C, Nicolosi G and Castelli F: ‘In vitro’ antioxidant and photoprotective properties and interaction with model membranes of three new quercetin esters. Eur J Pharm Biopharm. 56:167–174. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Gatto MT, Falcocchio S, Grippa E, Mazzanti G, Battinelli L, Nicolosi G, Lambusta D and Saso L: Antimicrobial and anti-lipase activity of quercetin and its C2-C163-O-acyl-esters. Bioorg Med Chem. 10:269–272. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Kumar V, Jahan F, Mahajan RV and Saxena RK: Efficient regioselective acylation of quercetin using Rhizopus oryzae lipase and its potential as antioxidant. Bioresour Technol. 218:1246–1248. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Sardone L, Pignataro B, Castelli F, Sarpietro MG, Nicolosi G and Marletta G: Temperature and pressure dependence of quercetin-3-O-palmitate interaction with a model phospholipid membrane: Film balance and scanning probe microscopy study. J Colloid Interface Sci. 271:329–335. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Yamauchi K, Mitsunaga T, Inagaki M and Suzuki T: Synthesized quercetin derivatives stimulate melanogenesis in B16 melanoma cells by influencing the expression of melanin biosynthesis proteins MITF and p38 MAPK. Bioorg Med Chem. 22:3331–3340. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Wuts PGM and Greene TW: Protection for Phenols and CatecholsGreene's Protective Groups in Organic Synthesis. John Wiley & Sons; New York: pp. 367–430. 2006, View Article : Google Scholar

20 

Bonina FP, Montenegro L, De Capraris P, Bousquet E and Tirendi S: 1-Alkylazacycloalkan-2-one esters as prodrugs of indomethacin for improved delivery through human skin. Int J Pharm. 77:21–29. 1991. View Article : Google Scholar

21 

Braumann T: Determination of hydrophobic parameters by reversed-phase liquid chromatography: Theory, experimental-techniques, and application in studies on quantitative structure-activity-relationships. J Chromatogr. 373:191–225. 1986. View Article : Google Scholar : PubMed/NCBI

22 

Mosawy S, Jackson DE, Woodman OL and Linden MD: Treatment with quercetin and 3′,4′-dihydroxyflavonol inhibits platelet function and reduces thrombus formation in vivo. J Thromb Thrombolys. 36:50–57. 2013. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Duan Y, Sun N, Xue M, Wang X and Yang H: Synthesis of regioselectively acylated quercetin analogues with improved antiplatelet activity. Mol Med Rep 16: 9735-9740, 2017.
APA
Duan, Y., Sun, N., Xue, M., Wang, X., & Yang, H. (2017). Synthesis of regioselectively acylated quercetin analogues with improved antiplatelet activity. Molecular Medicine Reports, 16, 9735-9740. https://doi.org/10.3892/mmr.2017.7781
MLA
Duan, Y., Sun, N., Xue, M., Wang, X., Yang, H."Synthesis of regioselectively acylated quercetin analogues with improved antiplatelet activity". Molecular Medicine Reports 16.6 (2017): 9735-9740.
Chicago
Duan, Y., Sun, N., Xue, M., Wang, X., Yang, H."Synthesis of regioselectively acylated quercetin analogues with improved antiplatelet activity". Molecular Medicine Reports 16, no. 6 (2017): 9735-9740. https://doi.org/10.3892/mmr.2017.7781
Copy and paste a formatted citation
x
Spandidos Publications style
Duan Y, Sun N, Xue M, Wang X and Yang H: Synthesis of regioselectively acylated quercetin analogues with improved antiplatelet activity. Mol Med Rep 16: 9735-9740, 2017.
APA
Duan, Y., Sun, N., Xue, M., Wang, X., & Yang, H. (2017). Synthesis of regioselectively acylated quercetin analogues with improved antiplatelet activity. Molecular Medicine Reports, 16, 9735-9740. https://doi.org/10.3892/mmr.2017.7781
MLA
Duan, Y., Sun, N., Xue, M., Wang, X., Yang, H."Synthesis of regioselectively acylated quercetin analogues with improved antiplatelet activity". Molecular Medicine Reports 16.6 (2017): 9735-9740.
Chicago
Duan, Y., Sun, N., Xue, M., Wang, X., Yang, H."Synthesis of regioselectively acylated quercetin analogues with improved antiplatelet activity". Molecular Medicine Reports 16, no. 6 (2017): 9735-9740. https://doi.org/10.3892/mmr.2017.7781
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team