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

• Published in: European journal of medicinal chemistry Vol. 211; p. 113112
• Main Authors: Mezeiova, Eva, Janockova, Jana, Andrys, Rudolf, Soukup, Ondrej, Kobrlova, Tereza, Muckova, Lubica, Pejchal, Jaroslav, Simunkova, Miriama, Handl, Jiri, Micankova, Petra, Capek, Jan, Rousar, Tomas, Hrabinova, Martina, Nepovimova, Eugenie, Marco-Contelles, Jose Luis, Valko, Marian, Korabecny, Jan
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 05.02.2021
• Subjects: Alzheimer Disease - drug therapy; Alzheimer’s disease; Amyloid-beta; Antioxidant; Drug Design; Humans; Inflammation; Monoamine oxidase; Multi-target directed ligand; Naphthoquinone; Naphthoquinones - pharmacology; Naphthoquinones - therapeutic use; Structure-Activity Relationship; Monoamine oxidase; Alzheimer’s disease; Multi-target directed ligand; Inflammation; Antioxidant; Naphthoquinone; Amyloid-beta
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2020.113112

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. [Display omitted] •Ten 2-propargylamino-naphthoquinones to tackle Alzheimer’s disease were designed.•Targeted compounds were effective against amyloid-beta aggregation.•Compounds inhibited monoamine oxidase A/B.•18 demonstrated a high anti-inflammatory response in SIM-A9 cells to LPS insult.•15 was classified as the top-ranked metal-chelating agent.