2. Academic Validation
  3. Design, synthesis and biological evaluation of novel carboline-cinnamic acid hybrids as multifunctional agents for treatment of Alzheimer's disease

Design, synthesis and biological evaluation of novel carboline-cinnamic acid hybrids as multifunctional agents for treatment of Alzheimer's disease

  • Bioorg Chem. 2020 Jun;99:103844. doi: 10.1016/j.bioorg.2020.103844.
Qinghong Liao 1,  Qi Li 2,  Yifan Zhao 1,  Pan Jiang 3,  Yuhui Yan 3,  Haopeng Sun 2,  Wenyuan Liu 4,  Feng Feng 5,  Wei Qu 6
Affiliations

Affiliations

  • 1 Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
  • 2 Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
  • 3 Jiangsu Food and Pharmaceutical Science College, Huaian 223003, China.
  • 4 Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.
  • 5 Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Food and Pharmaceutical Science College, Huaian 223003, China. Electronic address: fengfeng@cpu.edu.cn.
  • 6 Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: popoqzh@126.com.
PMID: 32325336 DOI: 10.1016/j.bioorg.2020.103844
Abstract

Alzheimer's disease (AD) is a complex neurodegenerative disease with multiple pathological features. Multifunctional compounds able to simultaneously interact with several pathological components have been considered as a solution to treat the complex pathologies of neurodegenerative diseases. β-carboline and cinnamic acid have been extensively studied for their widespread biological effects in treatment of AD, further application is limited due to its poor solubility and high toxicity. Herein, a series of carboline-cinnamic acid hybrids was designed and synthesized to obtain new multifunctional molecules with low toxicity and good physicochemical properties. In particular, e3 and e12 exhibited significant inhibition of Aβ aggregation (inhibitory rate at 25 μM: 65% and 72% respectively), moderate BuChE inhibition, excellent neuroprotective effects and low neurotoxicity. Furthermore, in the AD mice model, e3 and e12 could restore learning and memory function to a comparable level to that of the control and did not exhibit any acute toxicity in vivo at a relatively high dose of 600 mg/kg. Thus, these new compounds can be further studied as multifunctional molecules for AD.

Keywords

Alzheimer’s disease; Carboline-cinnamic acid hybrid; Neuroprotection; β-amyloid.

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