Conjugates of Tacrine with Salicylamide as Promising Multitarget Agents for Alzheimer's Disease

• DOI: 10.1002/cmdc.202200080
• Publication Date: 2022-03-24T21:44:45Z
• Authors: Maria V. Grishchenko; Galina F. Makhaeva; Yanina V. Burgart; Elena V. Rudakova; Natalia P. Boltneva; Nadezhda V. Kovaleva; Olga G. Serebryakova; Sofya V. Lushchekina; Tatiana Y. Astakhova; Ekaterina F. Zhilina; Evgeny V. Shchego...; Rudy J. Richardson; Victor I. Saloutin
• Keywords: Tacrine; Butyrylcholinesterase; Salicylamide; Lead compound; Docking (animal); IC50

Abstract New conjugates of tacrine and salicylamide with alkylene spacers were synthesized evaluated as potential multifunctional agents for Alzheimer's disease (AD). The compounds exhibited high acetylcholinesterase (AChE, IC 50 to 0.224 μM) butyrylcholinesterase (BChE, 0.0104 inhibitory activities. They also rather poor inhibitors carboxylesterase, suggesting a low tendency exert unwanted drug‐drug interactions in clinical use. mixed‐type reversible both cholinesterases demonstrated dual binding the catalytic peripheral anionic sites AChE molecular docking that, along experimental results on propidium iodide displacement, suggest their block AChE‐induced β ‐amyloid aggregation. new ABTS .+ ‐scavenging activity. N‐(6‐(1,2,3,4‐Tetrahydroacridin‐9‐ylamino)hexyl)salicylamide is lead compound that demonstrates metal chelating ability toward Cu 2+ , Fe Zn . Thus, have displayed be anti‐AD further development.