Synthesis, spectroscopic characterizations, DFT calculations and molecular docking studies of new quinoline-oxirane/piperidine/morpholine hybrids from quinoline gem-dicyanoepoxide

We report in this paper a combined experimental and theoretical study of new 2-quinolone-piperidine (5a) and -morpholine (5b-c) hybrids from3-(2-chloroquinolin-3-yl) oxirane-2,2-dicarbonitrile (3) via an epoxide ring opening reaction using appropriate synthetic routes. In a parallel approach, a tandem consecutive process was carried out, without isolation of the brominated intermediate for the synthesis of 2-quinolone-morpholine (5c). The prepared compounds were fully characterized by conventional analytical techniques, and single-crystal Xray diffraction for compound 5c was also reported. To increase the accuracy of experimental results, DFT and TDDFT calculations were performed including molecular structure optimization, NMR, optical and electronic data, frontier molecular orbitals and molecular descriptors. In addition, a molecular docking calculation was carried out to estimate the affinity between compounds 3, 5a, 5b and 5c and Acetylcholinesterase (AChE)/ Butyrylcholinesterase (BuChE). Theoretical results are in agreement with the experimental.

Automated summary

In this paper, a combined experimental and theoretical study was conducted to synthesize and characterize new 2-quinolone-piperidine and -morpholine hybrids. The results from experiments were validated using computational calculations, and the affinity between these compounds and Acetylcholinesterase/Butyrylcholinesterase was estimated through molecular docking.