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

doi:10.5246/jcps.2018.11.075

Abstract

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:

R916

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.

4aa

4ab

4ac

4ae

4ag

4aj

4ak

4al

4am

Ming He, Baohua Xie, Pei He, Haibing Zhou, Shengtang Huang, Chune Dong. 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[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(11): 735-752.

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