Six quinoline-piperonal hybrids were synthesized and evaluated as potential drugs against Alzheimer's disease (AD). Theoretical analysis of the pharmacokinetic and toxicological properties of the compounds suggest that they present good oral bio-availability and are also capable of penetrating the blood-brain barrier, qualifying as leads for new drugs against AD. Evaluation of their inhibitory capacity against acetyl- and butyrilcholinesterases (AChE and BChE) through Ellmann's test showed that three compounds present promising results with one of them being capable of inhibiting both enzymes. Further docking studies of the six compounds synthesized helped to elucidate the main interactions that may be responsible for the inhibitory activities observed.

Department of Chemistry Faculty of Science University of Hradec Kralove Rokitanskeho 62 50003 Hradec Kralové Czech Republic

Graduate Program in Adult Health Federal University of Maranhão Avenida dos Portugueses 1966 Vila Bacanga 65080 805 São Luís MA Brazil

Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense Military Institute of Engineering Praça General Tibúrcio 80 22290 270 Rio de Janeiro Brazil

Medicinal Chemistry Group Department of Chemistry Military Institute of Engineering Praça General Tibúrcio 80 22290 270 Rio de Janeiro RJ Brazil

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Are the current commercially available oximes capable of reactivating acetylcholinesterase inhibited by the nerve agents of the A-series?