Novel Uracil-Based Inhibitors of Acetylcholinesterase with Potency for Treating Memory Impairment in an Animal Model of Alzheimer’s Disease
Vyacheslav E. Semenov,
Irina V. Zueva,
Sofya V. Lushchekina,
Eduard G. Suleimanov,
Liliya M. Gubaidullina,
Marina M. Shulaeva,
Oksana A. Lenina,
Konstantin A. Petrov
Affiliations
Vyacheslav E. Semenov
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov str. 8, Kazan 420088, Russia
Irina V. Zueva
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov str. 8, Kazan 420088, Russia
Sofya V. Lushchekina
Emanuel Institute of Biochemical Physics, Kosygina st. 4, Moscow 119334, Russia
Eduard G. Suleimanov
Alexander Butlerov Institute of Chemistry, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kremlyovskaya str. 18, Kazan 420008, Russia
Liliya M. Gubaidullina
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov str. 8, Kazan 420088, Russia
Marina M. Shulaeva
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov str. 8, Kazan 420088, Russia
Oksana A. Lenina
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov str. 8, Kazan 420088, Russia
Konstantin A. Petrov
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov str. 8, Kazan 420088, Russia
Novel derivatives based on 6-methyluracil and condensed uracil, 2,4-quinazoline-2,4-dione, were synthesized with terminal meta- and para-benzoate moieties in polymethylene chains at the N atoms of the pyrimidine ring. In the synthesized compounds, the polymethylene chains were varied from having tris- to hexamethylene chains and quaternary ammonium groups; varying substituents (ester, salt, acid) at benzene ring were introduced into the chains and benzoate moieties. In vivo biological experiments demonstrated the potency of these compounds in decreasing the number of β-amyloid plaques and their suitability for the treatment of memory impairment in a transgenic model of Alzheimer’s disease.
