Research on Chemical Intermediates

, Volume 40, Issue 8, pp 3095–3107 | Cite as

Synthesis and antityrosinase, antioxidant activities of phloretin thiosemicarbazones

  • Binbin Xu
  • Yanying Yu
  • Pinghong Wan
  • Chunpeng Wan
  • Shuwen Cao


Three phloretin derivates were achieved through condensation of the phloretin template with thiosemicarbazide, 4-methylthiosemicarbazide, and 4-phenyl-3-thiosemicarbazide. Their purity was confirmed by high-performance liquid chromatograph and their structures were determined from their ultraviolet spectra, Fourier-transform infrared, 1H and 13C NMR, and mass spectra. The solubility of these novel compounds in ultrapure water at 25 °C was significantly improved compared with that of phloretin in the following order: phloretin thiosemicarbazone (PT, >1.00 mg/mL) > phloretin-4-phenyl-3-thiosemicarbazone (PPT, 0.52 mg/mL) > phloretin-4-methylthiosemicarbazone (PMT, 0.24 mg/mL) > phloretin (0.02 mg/mL). The tyrosinase inhibitory effect and various antioxidant assays in vitro were evaluated. Results showed that PT possesses potent tyrosinase inhibitory activity (IC50 = 57.81 ± 1.46 μM), which was better than phloretin (IC50 = 70.08 ± 0.88 μM). They also significantly quenched 1,1-diphenyl-2-picryl-hydrazyl and exhibited strong activity against the lipid peroxidation induced by Fe2+/ascorbic acid. Likewise, these compounds significantly protected against 2,2′-azo-bis(2-amidinopropane)dihydrochloride-induced Cu, Zn-superoxide dismutase, and pBR322 plasmid DNA damage in a dose-dependent manner.


Phloretin thiosemicarbazones Solubility Anti-tyrosinase Lipid peroxidation Cu, Zn-SOD Supercoiled pBR322 plasmid DNA 



This work was supported by the Natural Science Foundation of China (No. 20962014).


  1. 1.
    Y.K. Han, Y.J. Park, Y.M. Ha, D. Park, J.Y. Lee, N. Lee, J.H. Yoon, H.R. Moon, H.Y. Chung, BBA-Gen. Subj. 1820, 542 (2012)CrossRefGoogle Scholar
  2. 2.
    B. Fu, H. Li, X. Wang, F.S.C. Lee, S. Cui, J. Agric. Food Chem. 53, 7408 (2005)CrossRefGoogle Scholar
  3. 3.
    J.P. Zhang, Q.X. Chen, K.K. Song, J.J. Xie, Food Chem. 95, 579 (2006)CrossRefGoogle Scholar
  4. 4.
    M. Valko, M. Izakovic, M. Mazur, C.J. Rhodes, J. Telser, Mol. Cell. Biochem. 266, 37 (2004)CrossRefGoogle Scholar
  5. 5.
    K. Sachidanandam, S.C. Fagan, A. Ergul, Cardiovasc. Drug Rev. 23, 115 (2005)CrossRefGoogle Scholar
  6. 6.
    D. Harman, Age 6, 86 (1983)CrossRefGoogle Scholar
  7. 7.
    J.X. Wang, Z. Zhou, J.G. Wang, Flavour Fragr. Cosmet. 2, 4 (2002)Google Scholar
  8. 8.
    C. Remsberg, J. Yáñez, K. Vega-Villa, N. Davies, P. Andrews, J. Bioremed, Biodegradation 1, 101 (2010)Google Scholar
  9. 9.
    C.H. Wu, Y.S. Ho, C.Y. Tsai, Y.J. Wang, H. Tseng, P.L. Wei, C.H. Lee, R.S. Liu, S.Y. Lin, Int. J. Cancer 124, 2210 (2009)CrossRefGoogle Scholar
  10. 10.
    V. Stangl, M. Lorenz, A. Ludwig, N. Grimbo, C. Guether, W. Sanad, S. Ziemer, P. Martus, G. Baumann, K. Stangl, J. Nutr. 135, 172 (2005)Google Scholar
  11. 11.
    B.M. Choi, X.Y. Chen, S.S. Gao, R. Zhu, B.R. Kim, Pharmacol. Rep. 63, 708 (2011)CrossRefGoogle Scholar
  12. 12.
    J. Ma, X. Peng, K.M. Ng, C.M. Che, M. Wang, Food Funct. 3, 178 (2012)CrossRefGoogle Scholar
  13. 13.
    Y.J. Zhu, K.K. Song, Z.C. Li, Z.Z. Pan, Y.J. Guo, J.J. Zhou, Q. Wang, B. Liu, Q.X. Chen, J. Agric. Food Chem. 57, 5518 (2009)CrossRefGoogle Scholar
  14. 14.
    M. Singhal, A. Paul, H.P. Singh, S.K. Dubey, R.K. Songara, Int. J. Pharm. Sci. Drug Res. 3, 150 (2011)Google Scholar
  15. 15.
    G. Kumar, A. Kumar, N. Shishodia, Y. Garg, B. Yadav, E-J. Chem. 8, 1872 (1900)CrossRefGoogle Scholar
  16. 16.
    A.A. Al-Amiery, A.A.H. Kadhum, A.B. Mohamad, Bioinorg. Chem. Appl. 2012, 795812 (2012)CrossRefGoogle Scholar
  17. 17.
    J. Stariat, V. Šesták, K. Vávrová, M. Nobilis, Z. Kollárová, J. Klimeš, D.S. Kalinowski, D.R. Richardson, P. Kovaříková, Anal. Bioanal. Chem. 403, 309 (2012)CrossRefGoogle Scholar
  18. 18.
    D. Sriram, D. Banerjee, T.S.T.V.N. Varuna, M. Sankar, P. Yogeeswari, Med. Chem. Res. 21, 810 (2012)CrossRefGoogle Scholar
  19. 19.
    L.H. Chen, Y.H. Hu, W. Song, K.K. Song, X. Liu, Y.L. Jia, J.X. Zhuang, Q.X. Chen, J. Agric. Food Chem. 60, 1542 (2012)CrossRefGoogle Scholar
  20. 20.
    X.Y. Xie, L. Jiang, C.B. Xue, W.C. Luo, Huaxue Shiji 29, 34 (2007)Google Scholar
  21. 21.
    E.B. Erin, L.B. Julia, Cell Biochem. Biophys. 55, 1 (2009)CrossRefGoogle Scholar
  22. 22.
    B.M. Rezk, G.R.M.M. Haenen, W.J.F. van der Vijgh, A. Bast, Biochem. Biophys. Res. Commun. 295, 9 (2002)CrossRefGoogle Scholar
  23. 23.
    J.B. Liu, W. Yi, Y.Q. Wan, L. Ma, H.C. Song, Bioorg. Med. Chem. 16, 1096 (2008)CrossRefGoogle Scholar
  24. 24.
    K. Zhu, H. Zhou, H. Qian, Process Biochem. 41, 1296 (2006)CrossRefGoogle Scholar
  25. 25.
    Y. Çetinkaya, H. Göçer, A. Menzek, İ. Gülçin, Arch. Pharm. 345, 323 (2012)CrossRefGoogle Scholar
  26. 26.
    N. Belkheiri, B. Bouguerne, F. Bedos-Belval, H. Duran, C. Bernis, R. Salvayre, A. Nègre-Salvayre, M. Baltas, Eur. J. Med. Chem. 45, 3019 (2010)CrossRefGoogle Scholar
  27. 27.
    E. Ramachandran, S.P. Thomas, P. Poornima, P. Kalaivani, R. Prabhakaran, V.V. Padma, K. Natarajan, Eur. J. Med. Chem. 50, 405 (2012)CrossRefGoogle Scholar
  28. 28.
    G. Barrera, S. Pizzimenti, M.U. Dianzani, Mol. Aspects Med. 29, 1 (2008)CrossRefGoogle Scholar
  29. 29.
    Y. Qingming, P. Xianhui, K. Weibao, Y. Hong, S. Yidan, Z. Li, Z. Yanan, Y. Yuling, D. Lan, L. Guoan, Food Chem. 118, 84 (2010)CrossRefGoogle Scholar
  30. 30.
    J.H. Kang, K.S. Kim, S.Y. Choi, H.Y. Kwon, M.H. Won, T.C. Kang, BBA-Gen. Subj. 1570, 89 (2002)CrossRefGoogle Scholar
  31. 31.
    G.M. Ehrenfeld, J.B. Shipley, D.C. Heimbrook, H. Sugiyama, E.C. Long, J.H. Van Boom, G.A. Van der Marel, N.J. Oppenheimer, S.M. Hecht, Biochemistry 26, 931 (1987)CrossRefGoogle Scholar
  32. 32.
    P. Zhang, S. Omaye, Food Chem. Toxicol. 39, 239 (2001)CrossRefGoogle Scholar
  33. 33.
    T.C. Bai, G.B. Yan, J. Hu, H.L. Zhang, C.G. Huang, Int. J. Pharm. 308, 100 (2006)CrossRefGoogle Scholar
  34. 34.
    Y.L. Lee, J.H. Yang, J.L. Mau, Food Chem. 106, 1128 (2008)CrossRefGoogle Scholar
  35. 35.
    N. KaralI, Ö. Güzel, N. Özsoy, S. Özbey, A.I. Salman, Eur. J. Med. Chem. 45, 1068 (2010)CrossRefGoogle Scholar
  36. 36.
    H.Y. Kwon, S.Y. Choi, M.H. Won, T.C. Kang, J.H. Kang, BBA-Protein Struct. Mol. Enzymol. 1543, 69 (2000)CrossRefGoogle Scholar
  37. 37.
    X. Lin, D.J. Yang, W.Q. Cai, Q.Y. Zhao, Y.F. Gao, Q. Chen, R. Wang, BBA-Mol. Basis Dis. 1639, 195 (2003)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Binbin Xu
    • 1
  • Yanying Yu
    • 2
  • Pinghong Wan
    • 1
  • Chunpeng Wan
    • 3
  • Shuwen Cao
    • 1
    • 2
  1. 1.State Key Laboratory of Food Science and TechnologyNanchang UniversityNanchangPeople’s Republic of China
  2. 2.Department of ChemistryNanchang UniversityNanchangPeople’s Republic of China
  3. 3.College of AgronomyJiangxi Agricultural UniversityNanchangPeople’s Republic of China

Personalised recommendations