Synthesis, biological evaluation and molecular docking study of 7-amine-spiro[chromeno[4,3-b]quinoline-6,1′-cycloalkanes] as new tacrine hybrids

This Letter reports the first series of seven examples of novel 7-amine-spiro[chromeno[4,3-b]quinoline-6,1'-cycloalkanes], where cycloalkane is cyclopentane, cyclohexane, cycloheptane, 2-methyl-, 3-methyl-, 4-methyl-, and 4-t-butyl-cyclohexane. These new compounds were synthesized at yields of 30-65% by a one-pot cyclocondensation reaction of 2-aminobenzonitrile and seven examples of spiro[chroman-2,1'-cycloalkan]-4-ones, using AlCl3 as the catalyst, without solvent and under conventional thermal heating. Subsequently, these spirochromeno-quinolines were subjected to AChE and cytotoxicity activity, and molecular docking studies. Both results for these new tacrine analogues were correlated with the structural features and showed the best results for the tacrine hybrid that possesses the spirocyclopentane moiety. (C) 2015 Elsevier Ltd. All rights reserved.