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Pregled bibliografske jedinice broj: 1219548

Design, synthesis and biological evaluation of biscarbamates as potential selective butyrylcholinesterase inhibitors fot the treatment of Alzheimer`s disease


Matošević, Ana; Knežević, Anamarija; Zandona, Antonio; Maraković, Nikola; Kovarik, Zrinka; Bosak, Anita
Design, synthesis and biological evaluation of biscarbamates as potential selective butyrylcholinesterase inhibitors fot the treatment of Alzheimer`s disease // Pharmaceuticals, 15 (2022), 10; 1220, 24 doi:10.3390/ph15101220 (međunarodna recenzija, članak, znanstveni)


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Naslov
Design, synthesis and biological evaluation of biscarbamates as potential selective butyrylcholinesterase inhibitors fot the treatment of Alzheimer`s disease

Autori
Matošević, Ana ; Knežević, Anamarija ; Zandona, Antonio ; Maraković, Nikola ; Kovarik, Zrinka ; Bosak, Anita

Izvornik
Pharmaceuticals (1424-8247) 15 (2022), 10; 1220, 24

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
acetylcholinesterase ; metal chelating ; detailed kinetic study ; spontaneous decarbamylation ; rate constants ; molecular docking

Sažetak
As butyrylcholinesterase (BChE) plays a role in the progression of symptoms and pathophysiology of Alzheimer’s disease (AD), selective inhibition of BChE over acetylcholinesterase (AChE) can represent a promising pathway in treating AD. The carbamate group was chosen as a pharmacophore because the carbamates currently or previously in use for the treatment of AD displayed significant positive effects on cognitive symptoms. Eighteen biscarbamates with different substituents at the carbamoyl and hydroxyaminoethyl chain were synthesized, and their inhibitory potential toward both cholinesterases and inhibition selectivity were determined. The ability of carbamates to cross the blood–brain barrier (BBB) by passive transport, their cytotoxic profile and their ability to chelate biometals were also evaluated. All biscarbamates displayed a time-dependent inhibition with inhibition rate constants within 10−3–10−6 M−1 min−1 range for both cholinesterases, with generally higher preference to BChE. For two biscarbamates, it was determined that they should be able to pass the BBB by passive transport, while for five biscarbamates, this ability was slightly limited. Fourteen biscarbamates did not exhibit a cytotoxic effect toward liver, kidney and neuronal cells. In conclusion, considering their high BChE selectivity, non-toxicity, ability to chelate biometals and pass the BBB, compounds 2 and 16 were pointed out as the most promising compounds for the treatment of middle and late stages of AD.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija



POVEZANOST RADA


Projekti:
IP-2018-01-7683 - Analiza interakcija butirilkolinesteraze s novim inhibitorima i reaktivatorima (AnalyseBChE) (Kovarik, Zrinka, HRZZ - 2018-01) ( CroRIS)
HRZZ-IP-2020-02-9343 - Razvoj bioaktivnih molekula za tretman neurodegenerativnih bolesti (BioMol4ND) (Bosak, Anita, HRZZ - 2020-02) ( CroRIS)

Ustanove:
Institut za medicinska istraživanja i medicinu rada, Zagreb,
Institut "Ruđer Bošković", Zagreb

Poveznice na cjeloviti tekst rada:

doi www.mdpi.com

Citiraj ovu publikaciju:

Matošević, Ana; Knežević, Anamarija; Zandona, Antonio; Maraković, Nikola; Kovarik, Zrinka; Bosak, Anita
Design, synthesis and biological evaluation of biscarbamates as potential selective butyrylcholinesterase inhibitors fot the treatment of Alzheimer`s disease // Pharmaceuticals, 15 (2022), 10; 1220, 24 doi:10.3390/ph15101220 (međunarodna recenzija, članak, znanstveni)
Matošević, A., Knežević, A., Zandona, A., Maraković, N., Kovarik, Z. & Bosak, A. (2022) Design, synthesis and biological evaluation of biscarbamates as potential selective butyrylcholinesterase inhibitors fot the treatment of Alzheimer`s disease. Pharmaceuticals, 15 (10), 1220, 24 doi:10.3390/ph15101220.
@article{article, author = {Mato\v{s}evi\'{c}, Ana and Kne\v{z}evi\'{c}, Anamarija and Zandona, Antonio and Marakovi\'{c}, Nikola and Kovarik, Zrinka and Bosak, Anita}, year = {2022}, pages = {24}, DOI = {10.3390/ph15101220}, chapter = {1220}, keywords = {acetylcholinesterase, metal chelating, detailed kinetic study, spontaneous decarbamylation, rate constants, molecular docking}, journal = {Pharmaceuticals}, doi = {10.3390/ph15101220}, volume = {15}, number = {10}, issn = {1424-8247}, title = {Design, synthesis and biological evaluation of biscarbamates as potential selective butyrylcholinesterase inhibitors fot the treatment of Alzheimer`s disease}, keyword = {acetylcholinesterase, metal chelating, detailed kinetic study, spontaneous decarbamylation, rate constants, molecular docking}, chapternumber = {1220} }
@article{article, author = {Mato\v{s}evi\'{c}, Ana and Kne\v{z}evi\'{c}, Anamarija and Zandona, Antonio and Marakovi\'{c}, Nikola and Kovarik, Zrinka and Bosak, Anita}, year = {2022}, pages = {24}, DOI = {10.3390/ph15101220}, chapter = {1220}, keywords = {acetylcholinesterase, metal chelating, detailed kinetic study, spontaneous decarbamylation, rate constants, molecular docking}, journal = {Pharmaceuticals}, doi = {10.3390/ph15101220}, volume = {15}, number = {10}, issn = {1424-8247}, title = {Design, synthesis and biological evaluation of biscarbamates as potential selective butyrylcholinesterase inhibitors fot the treatment of Alzheimer`s disease}, keyword = {acetylcholinesterase, metal chelating, detailed kinetic study, spontaneous decarbamylation, rate constants, molecular docking}, chapternumber = {1220} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus


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