Design, synthesis, and multitarget evaluation of novel quinolone-based heterocyclic derivatives as acetyl cholinesterase inhibitors for Alzheimer’s disease therapy

Abstract Background Alzheimer disease is progressive neurodegenerative disorder with mild memory loss and cognitive impairment. Neurodegenerative diseases in which the decrease in the acetylcholine is observed are growing worldwide. Ten quinolone containing compounds were synthesized and screened for acetylcholine inhibition and Aβ fibril formation inhibition. Materials and methods The newly developed compounds were synthesized. Numerous methods (IR, NMR, Mass spectroscopy, etc.,) were used to characterize these substances. In silico study was performed for receptor–drug interaction with acetylcholine and Aβ fibril protein, and ADMET prediction was done for drug-like properties. In vitro Ellman assay and in vivo screening of synthesized compounds were done by using different animal model. Results Anticholinesterase screening results identified compounds D1 and D6 as the most effective of the series. It is the most effective compound screened for vivo studies. The results of molecular docking revealed significant interactions at the active site of cholinesterase Val294, Phe296, Phe297, Typ33, His287, and Aβ fibril protein; the outcomes were good and in agreement with in vivo findings. Conclusion The study’s findings showed that some substances had promising anti-Alzheimer’s properties that were comparable to those of the standard drug. The highly active novel anti-Alzheimer analogues may therefore represent a possible lead, and additional studies may result in a potential new drug candidate. Graphical abstract