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Pregled bibliografske jedinice broj: 1136179

Adamantane based derivatives as reversible inhibitors of human AChE and BChE


Komatović, Katarina; Matošeivć, Ana; Terzić- Jovanović, Nataša; Bosak, Anita; Opsenica, Dejan
Adamantane based derivatives as reversible inhibitors of human AChE and BChE // FEBS Open Bio "45th FEBS Congress, Molecules of Life: Towards New Horizons", Ljubljana, Slovenia, July 3–8, 2021
Ljubljana, 2021. str. 213-213 (poster, međunarodna recenzija, sažetak, znanstveni)


CROSBI ID: 1136179 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Adamantane based derivatives as reversible inhibitors of human AChE and BChE

Autori
Komatović, Katarina ; Matošeivć, Ana ; Terzić- Jovanović, Nataša ; Bosak, Anita ; Opsenica, Dejan

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
FEBS Open Bio "45th FEBS Congress, Molecules of Life: Towards New Horizons", Ljubljana, Slovenia, July 3–8, 2021 / - Ljubljana, 2021, 213-213

Skup
Virtual 45th FEBS Congress, Molecules of Life: Towards New Horizons

Mjesto i datum
Ljubljana, Slovenija, 3-8.07.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Adamantane ; acetylcholinesterase ; butyrylcholinesterase ; Alzheimer`s disease

Sažetak
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are two related enzymes responsible to control the level of neurotransmitters. Acetylcholine (ACh) is removed from cholinergic synapse by enzymatic hydrolysis with AChE, which leads to termination of impulse transmission. Both, AChE and BChE, are identified as targets in the treatment of neurodegenerative disorders, such as Alzheimer’s disease (AD). The most used approach in finding new drugs for the treatment of AD is the inhibition of AChE. We synthesized a series of 4- aminoquinoline derivatives of adamantane with different linkers between two subunits, based on the highly active and selective cholinesterase inhibitor with adamantane.1 Compounds were tested as inhibitors of human AChE and BChE, with acetylthiocholine (ATCh) as the substrate for enzyme activity measurements. AChE and BChE activity toward ATCh decreased in the presence of all tested compounds. Inhibition potency of tested compounds expressed as enzyme-inhibitor complex dissociation constant (Ki), ranged from 0.1 to 4.2 μM for AChE and from 0.1 to 7.8 μM for BChE. Changing the length of the linker, structural isomerization and their conformation freedom, we influenced the inhibition potency of compounds, as well as their BChE / AChE selectivity. Increasing of steric demand of molecule resulted in a decrease of inhibitory activity. The compound with n-octyl alkyl chain between quinoline and adamantyl fragments has the lowest Ki values which are approximately 8 and 39 times lower for AChE and BChE respectively than previously tested derivative. [1] Docking simulations showed that adamantyl fragment achieved additional interactions with amino acids residues indicating that adamantane scaffold is important for inhibition of cholinesterase activity, aside from aminoquinoline pharmacophore.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija



POVEZANOST RADA


Ustanove:
Institut za medicinska istraživanja i medicinu rada, Zagreb

Profili:

Avatar Url Ana Matošević (autor)

Avatar Url Anita Bosak (autor)


Citiraj ovu publikaciju

Komatović, Katarina; Matošeivć, Ana; Terzić- Jovanović, Nataša; Bosak, Anita; Opsenica, Dejan
Adamantane based derivatives as reversible inhibitors of human AChE and BChE // FEBS Open Bio "45th FEBS Congress, Molecules of Life: Towards New Horizons", Ljubljana, Slovenia, July 3–8, 2021
Ljubljana, 2021. str. 213-213 (poster, međunarodna recenzija, sažetak, znanstveni)
Komatović, K., Matošeivć, A., Terzić- Jovanović, N., Bosak, A. & Opsenica, D. (2021) Adamantane based derivatives as reversible inhibitors of human AChE and BChE. U: FEBS Open Bio "45th FEBS Congress, Molecules of Life: Towards New Horizons", Ljubljana, Slovenia, July 3–8, 2021.
@article{article, year = {2021}, pages = {213-213}, keywords = {Adamantane, acetylcholinesterase, butyrylcholinesterase, Alzheimer`s disease}, title = {Adamantane based derivatives as reversible inhibitors of human AChE and BChE}, keyword = {Adamantane, acetylcholinesterase, butyrylcholinesterase, Alzheimer`s disease}, publisherplace = {Ljubljana, Slovenija} }
@article{article, year = {2021}, pages = {213-213}, keywords = {Adamantane, acetylcholinesterase, butyrylcholinesterase, Alzheimer`s disease}, title = {Adamantane based derivatives as reversible inhibitors of human AChE and BChE}, keyword = {Adamantane, acetylcholinesterase, butyrylcholinesterase, Alzheimer`s disease}, publisherplace = {Ljubljana, Slovenija} }




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