Abu-Aisheh_2019_Heliyon_5_e01552

Reference

Title : Coumarin derivatives as acetyl- and butyrylcholinestrase inhibitors: An in vitro, molecular docking, and molecular dynamics simulations study - Abu-Aisheh_2019_Heliyon_5_e01552
Author(s) : Abu-Aisheh MN , Al-Aboudi A , Mustafa MS , El-Abadelah MM , Ali SY , Ul-Haq Z , Mubarak MS
Ref : Heliyon , 5 :e01552 , 2019
Abstract :

Alzheimer's disease is an irreversible and progressive brain disease that can cause problems with memory and thinking skills. It is characterized by loss of cognitive ability and severe behavioral abnormalities, and could lead to death. Cholinesterases (ChEs) play a crucial role in the control of cholinergic transmission, and subsequently, the acetylcholine level in the brain is upgraded by inhibition of ChEs. Coumarins have been shown to display potential cholinesterase inhibitory action, where the aromatic moiety has led to the design of new candidates that could inhibit Abeta aggregation. Accordingly, the present work is an in vitro activity, along with docking and molecular dynamics (MD) simulation studies of synthesized coumarin derivatives, to explore the plausible binding mode of these compounds inside the cholinesterase enzymes. For this purpose, a series of previously prepared N1-(coumarin-7-yl) derivatives were screened in vitro for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. The assayed compounds exhibited moderate inhibitory activity against AChE, with IC50 values ranging from 42.5 +/- 2.68 to 442 +/- 3.30 muM. On the other hand, the studied compounds showed remarkable activity against BChE with IC50 values ranging from 2.0 +/- 1.4 nM to 442 +/- 3.30 muM. In order to better understand the ligand binding site interaction of compounds and the stability of protein-ligand complexes, a molecular docking with molecular dynamics simulation of 5000 ps in an explicit solvent system was carried out for both cholinesterases. We concluded that the tested coumarin derivatives are potential candidates as leads for potent and efficacious ChEs inhibitors.

PubMedSearch : Abu-Aisheh_2019_Heliyon_5_e01552
PubMedID: 31183424

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Citations formats

Abu-Aisheh MN, Al-Aboudi A, Mustafa MS, El-Abadelah MM, Ali SY, Ul-Haq Z, Mubarak MS (2019)
Coumarin derivatives as acetyl- and butyrylcholinestrase inhibitors: An in vitro, molecular docking, and molecular dynamics simulations study
Heliyon 5 :e01552

Abu-Aisheh MN, Al-Aboudi A, Mustafa MS, El-Abadelah MM, Ali SY, Ul-Haq Z, Mubarak MS (2019)
Heliyon 5 :e01552