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Chinese Journal of Organic Chemistry >

2017 , Vol. 37 >Issue 4: 873 - 880

DOI: https://doi.org/10.6023/cjoc201611026

ARTICLE

Design Synthesis of Gardenamide A/Tacrine Hybrids and Their Protection against 6-Hydroxydopamine-Induced Insults in PC12 Cells

  • Zhang Xinyi ,
  • Yuan Sheng ,
  • Zhao Jiaqiang ,
  • Zhang Lei ,
  • Zhang Chao ,
  • Wang Rikang ,
  • Chen Heru
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  • a. Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632;
    b. National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006;
    c. Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632

Received date: 2016-11-22

  Revised date: 2017-03-01

  Online published: 2017-03-03

Supported by

Project supported by the Natural Science Foundation of Guangdong Province (No. 2015A030311012) and the Natural Science Foundation of Jiangxi Province (No. 20151BAB215030).

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Abstract

Seven gardenamide A (GA)/tacrine hybrids have been designed and synthesized. Firstly, 10-gardenamide A (DG) aldehyde was prepared through 5 steps reactions applied genipin as starting material. The overyield was 20.4%. Then, N-terminated aminoalkyltacrine (TN-n) was synthesized via 4 steps reactions started from o-aminobenzoic acid. The overall yield was 50.0%~65.4%. After that, DG reacted with TN-n at the presence of appropriate reductant leading to the target compounds. The yields were from 37% to 54%. The structures of all the target compounds were confirmed by 1H NMR, 13C NMR and ESI-MS. The bioactivities of all the hybrids were evaluated by setting up 6-hydroxydopamine-induced impaired PC12 cell model. It was indicated that two hybrids TNG-1 and TNG-5 showed better neuroprotective activity than tacrine, GA or their combination. Based on this fact, it was proposed that the hybrids TNG-1 and TNG-5 were better drug-like candidates than both monomers.

Key words： drug design; drug synthesis; gardenamide A; tacrine; alzheimer disease

Cite this article

Zhang Xinyi , Yuan Sheng , Zhao Jiaqiang , Zhang Lei , Zhang Chao , Wang Rikang , Chen Heru . Design Synthesis of Gardenamide A/Tacrine Hybrids and Their Protection against 6-Hydroxydopamine-Induced Insults in PC12 Cells[J]. Chinese Journal of Organic Chemistry, 2017 , 37(4) : 873 -880 . DOI: 10.6023/cjoc201611026

References

[1] Zimmermann, G. R.; Lehar, J.; Keith, C. T. Drug Discovery Today 2007, 12, 34.
[2] Hanauske, A. R.; Chen, V.; Peoletti, P. Oncologist 2001, 6, 363.
[3] Graul, A.; Leeson, P.; Castaner, J. Drugs Future 1999, 24, 269.
[4] Sorbera, L. A.; Castaner, J.; Fresno, M. Drugs Future 2002, 27, 132.
[5] Geldenhuys, W. J.; Youdim, M. B. H.; Carroll, R. T.; Van der Schyf, C. J. Prog. Neurobiol. 2011, 94, 347.
[6] Pang, Y. P.; Cusack, B.; Groshan, K.; Richelson, E. J. Biol. Chem. 1996, 271, 15060.
[7] Bolognesi, M. L.; Cavalli, A.; Valgimigli, L. J. Med. Chem. 2007, 50, 6446.
[8] Fernandez, M. I.; Perez, C.; Campillo, N. E. ChemMedChem 2009, 4, 828.
[9] Luo, J.; Wang, J.; Huang, Z.; Yang, J.; Yao, X.; Chen, H.; Zheng, W. ChemMedChem 2012, 7, 1661.
[10] Wang, J.; Yang, J.; Peng, L.; Zhao, J.; Mu, N.; Huang, J.; Lazarovici, P.; Chen, H.; Zheng, W. Neuroscience 2015, 286, 242.
[11] Wang, J.; Peng, L.; Zhao, J.; Zhang, L.; Guo, C.; Zheng, W.; Chen, H. Int. J. Mol. Sci. 2015, 16, 22350.
[12] Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
[13] Dess, D. B.; Martin, J. C. J. Am. Chem Soc.. 1991, 113, 7277.
[14] Carlier, P. R.; Han, Y. F.; Chow, E. S.-H.; Li, C. P.-L.; Wang, H.; Lieu, T. X.; Wong, H. S.; Pang, Y.-P. Bioorg. Med. Chem. 1999, 7, 351.
[15] Zhou, J. J.; Huang, H.; Xie, S. Q. Chin. Chem. Lett. 2008, 19, 99.
[16] Sheibley, F. E. J. Chem. Educ. 1943, 20, 115.

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