2-Propargylamino-naphthoquinone derivatives as multipotent agents for the treatment of Alzheimer's disease

Alzheimer's disease is a progressive brain disorder with characteristic symptoms and several pathological hallmarks. The concept of “one drug, one target” has not generated any new drugs since 2004. The new era of drug development in the field of AD builds upon rationally designed multi-target directed ligands that can better address the complexity of AD. Herewith, we designed ten novel derivatives of 2-propargylamino-naphthoquinone. The biological evaluation of these compounds includes inhibition of monoamine oxidase A/B, inhibition of amyloid-beta aggregation, radical-scavenging, and metal-chelating properties. Some of the compounds possess low cytotoxicity profile with an anti-inflammatory ability in the lipopolysaccharide-stimulated cellular model. All these features warrant their further testing in the field of AD.This work was supported by a grant of the Ministry of Defence “Long Term Development Plan” Medical Aspects of Weapons of Mass Destruction of the Faculty of Military Health Sciences, University of Defence; by the Ministry of Education, Youth and Sports of Czech Republic (project ERDF IT4N no. CZ.02.1.01/0.0/0.0/ 18_069/0010054), by EU COST Action (CA15135: “Multi-target paradigm for innovative ligand identification in the drug discovery process (MuTaLig)"), and by MH CZ - DRO (University HospitalHradec Kralove, No. 00179906). We also thank the Scientific Grant Agency (VEGA Project 1/0482/20) and Research and Development Support Agency (APVV-15-0079 and APVV-19-0087). Marvin was used for drawing, displaying, and characterizing chemical structures, substructures and reactions, Marvin 20.15.0, ChemAxon (https://www.chemaxon.com)