Chin. J. Org. Chem. ›› 2014, Vol. 34 ›› Issue (1): 137-146.DOI: 10.6023/cjoc201305040 Previous Articles     Next Articles

Articles

6-(烷胺酰肼基)-1-氮杂苯并蒽酮衍生物的合成及生物活性研究

钟书明, 卫沈旗, 刘允, 唐煌   

  1. 广西师范大学化学化工学院 药用资源化学与药物分子工程教育部重点实验室 桂林 541004
  • 收稿日期:2013-05-25 修回日期:2013-09-13 发布日期:2013-09-25
  • 通讯作者: 唐煌 E-mail:hyhth@163.com
  • 基金资助:

    国家自然科学基金(Nos. 81260471);广西自然科学基金(No. 2013GXNSFAA019038);药用资源化学与药物分子工程教育部重点实验室(No. CMEMR2012-A05)资助项目.

Synthesis and Biological Evaluation of 6-[(Alkylamino)-hydrazide-yl]-1-azabenzanthrone Derivatives

Zhong Shuming, Wei Shenqi, Liu Yun, Tang Huang   

  1. Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources of Ministry of Education, School of Chemistry & Chemical Engineering, Guangxi Normal University, Guilin 541004
  • Received:2013-05-25 Revised:2013-09-13 Published:2013-09-25
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 81260471), the Natural Science Foundation of Guangxi Province (No. 2013GXNSFAA019038) and the Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Education (No. CMEMR2012-A05).

A series of novel 6-substituted 1-azabenzanthrone derivatives have been designed and synthesized from 4-chlorophenethylamine and phthalic anhydride. Their abilities to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and AChE-induced β-amyloid (Aβ) aggregation were also tested. The synthetic compounds exhibited moderate cholinesterase inhibitory activity with IC50 values in the micromolar range in most cases. Non-competitive inhibition was found for these derivatives to AChE by the graphical analysis of steady-state inhibition data. Moreover, all compounds exhibited significant inhibitory activity on AChE-induced Aβ aggregation with inhibitory potency from 35.3% to 62.2%. Finally, eleven out of eighteen synthetic compounds were predicted to be able to cross the blood-brain barrier (BBB) to reach their targets in the central nervous system (CNS) according to a parallel artificial membrane permeation assay.

Key words: 1-azabenzanthrone derivative, synthesis, β-amyloid, acetylcholinesterase inhibitor, blood-brain barrier