http://www.jcps.ac.cn

Journal of Chinese Pharmaceutical Sciences ›› 2018, Vol. 27 ›› Issue (11): 735-752.DOI: 10.5246/jcps.2018.11.075

• Original articles •     Next Articles

Design, synthesis and biological evaluation of novel quinoline [4,3-b]chromene derivatives as AChE inhibitors through an efficient one-pot, four-component microwave-mediated reaction

Ming He1, Baohua Xie1, Pei He1, Haibing Zhou1*, Shengtang Huang2*, Chune Dong1*   

  1. 1. Hubei Province Key Laboratory of Allergy and Immunology, State Key Laboratory of Virology, Hubei Province Engineering and Technology Research Centre for Fluorinated Pharmaceuticals, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China
    2. School of Pharmacy, Hubei University of Science and Technology, Xianning 437100, China
  • Received:2018-03-18 Revised:2018-05-29 Online:2018-11-28 Published:2018-09-17
  • Contact: Tel.: +86-027-68759586, E-mail: zhouhb@whue.du.cn; cdong@whu.edu.cn; huangst6511@hbust.edu.cn
  • Supported by:
    NSFC (Grant No. 81773557, 81573279, 81373255), Major Project of Technology Innovation Program of Hubei Province (Grant No. 2016ACA126), NSFHP (Grant No. 2017CFA024), and the Fundamental Research Funds for the Central Universities of China (Grant No. 2042017kf0288).

Abstract:

An efficient synthesis of chromeno[4,3-b]quinoline derivatives via one-pot, four-component reaction of 4-hydroxycoumarin, formaldehyde, cyclohexanedione, ammonium ceric nitrate under microwave irradiation was accomplished. The structures of these compounds were unambiguously confirmed by single crystal X-ray diffraction. Furthermore, the anti-AChE activities of these compounds in vitro were investigated at concentrations of 20 μM and 50 μM by using a standard Ellman’s method. The relationship of inhibitory activities and structures of these chromeno [4,3-b]quinolines was also systematically studied. Of all the compounds investigated, 4ag emerged as the most potent AChE inhibitor with IC50 values of 5.63 µM, and it might be used as potent lead for the development anti-AChE agents. Moreover, molecular modelling was conducted to understand the optimal interaction of AChE with these types of compounds.

Key words: Chromeno [4,3-b]quinoline, Anti-AChE activities, Molecular modelling, Four-component reaction

CLC Number: 

Supporting:

1. X-ray Crystallographic Data for Compound 4e.
Table S1. Crystal data and structure refinement for 4e
 
 
Table S2. Atomic coordinates ( x104) and equivalent isotropic displacement parameters (?2x103) for mo_180320C_0m. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.
 
 
Table S3. Bond lengths for mo_180320C_0m.
 
Symmetry transformations used to generate equivalent atoms. 
 
Table S4. Anisotropic displacement parameters (?2x103) for mo_180320C_0m. The anisotropic displacement factor exponent takes the form: -2p2[ h2 a*2U11 + ... + 2 h k a* b* U12 ]
 
 
Table S5. Hydrogen coordinates ( x104) and isotropic displacement parameters (?2x10 3) for mo_180320C_0m.
 
 
Table S6. Torsion angles for mo_180320C_0m.
  
Symmetry transformations used to generate equivalent atoms. 
 
Table S7. Hydrogen bonds for mo_180320C_0m.
 
Symmetry transformations used to generate equivalent atoms:
#1 x-1,y,z    #2 -x+2,-y,-z+1 
 
 
2. RepresentativeNMR Spectra of Chromeno[4,3-b]quinoline Derivatives 4. 
 
4a
 
 
4b
 
 
4c
 
 
4d
 
 
4e
 
 
4f
 
 
4g
 
 
4h
 
 
4i
 
 
4j
 
 
4k
 
 
4l
 
 
4m
 
 
4n
 
 
4o
 
 
4p
 
 
4q
 
 
4r
 
 
4s
 
 
4u
 
 
4v
 
 
4w
 
 
4z
 
 
4aa
 
 
4ab
 
 
4ac
 
 
4ae
 
 
4ag
 
 
4aj
 
 
4ak
 
 
4al
 
 
4am