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

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.