Citation: 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 shu

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

Zhang Xinyi ^a ,
Yuan Sheng ^a ,
Zhao Jiaqiang ^a ,
Zhang Lei ^a ,
Zhang Chao ^a ,
Wang Rikang ^b ,
Chen Heru ^a,c,*,,

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

Corresponding author: Chen Heru, thrchen@jnu.edu.cn
Received Date: 22 November 2016
Revised Date: 1 March 2017

Fund Project: the Natural Science Foundation of Guangdong Province 2015A030311012the Natural Science Foundation of Jiangxi Province 20151BAB215030

Figures(3)

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.
- drug design,
- drug synthesis,
- gardenamide A,
- tacrine,
- alzheimer disease
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