MicroRNA regulators of cholinergic signaling link neuromuscular, cardiac and metabolic systems

Pienica, Claudia; Soreq, Hermona

doi:10.18054/pb.v118i4.4472

Cited by 2 publications

(2 citation statements)

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“…AChE has an essential physiological role in the body as it controls the transmission of nerve impulses in the cholinergic synapses of the central and peripheral nervous system by hydrolysis of the neurotransmitter acetylcholine. It also has a role in neuritogenesis, cell adhesion, proliferation and cell interactions, synaptogenesis, dopamine neuronal activation, the formation of amyloid fibres characteristic for Alzheimer's disease, haematopoiesis and thrombopoiesis [7][8][9] . The role of BChE is not physiologically essential but it could be assigned to the detoxification of xenobiotics (organophosphates and carbamate pesticides, cocaine, aspirin, succinyldicholine, etc.)…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and cholinesterase inhibitory properties of new oxazole benzylamine derivatives

Šagud

Hrvat

Grgičević

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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The enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are primary targets in attenuating the symptoms of neurodegenerative diseases. Their inhibition results in elevated concentrations of the neurotransmitter acetylcholine which supports communication among nerve cells. It was previously shown for trans-4/5-arylethenyloxazole compounds to have moderate AChE and BChE inhibitory properties. A preliminary docking study showed that elongating oxazole molecules and adding a new NH group could make them more prone to bind to the active site of both enzymes. Therefore, new trans-amino-4-/5-arylethenyl-oxazoles were designed and synthesised by the Buchwald-Hartwig amination of a previously synthesised trans-chloro-arylethenyloxazole derivative. Additionally, naphthoxazole benzylamine photoproducts were obtained by efficient photochemical electrocyclization reaction. Novel compounds were tested as inhibitors of both AChE and BChE. All of the compounds exhibited binding preference for BChE over AChE, especially for trans-amino-4-/5-arylethenyl-oxazole derivatives which inhibited BChE potently (IC 50 in mM range) and AChE poorly (IC 50)100 mM). Therefore, due to the selectivity of all of the tested compounds for binding to BChE, these compounds could be applied for further development of cholinesterase selective inhibitors. HIGHLIGHTS Series of oxazole benzylamines were designed and synthesised The tested compounds showed binding selectivity for BChE Naphthoxazoles were more potent AChE inhibitors ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

Design, synthesis and cholinesterase inhibitory properties of new oxazole benzylamine derivatives

Šagud

Hrvat

Grgičević

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Enzyme AChE plays an indispensable physiological role in the body controlling the channeling of nerve impulses in the cholinergic synapses of the central and peripheral nervous system by hydrolysis of the neurotransmitter acetylcholine. Moreover, AChE takes part in many other processes, for instance, dopamine neuronal activation and the formation of amyloid fibers characteristic of Alzheimer’s disease [ 7 , 8 , 9 ]. The role of BChE is appointed to the catalytic and stoichiometric detoxification of xenobiotics (for example, organophosphates, cocaine, aspirin, etc.)…”

Section: Introductionmentioning

confidence: 99%

New Thienobenzo/Naphtho-Triazoles as Butyrylcholinesterase Inhibitors: Design, Synthesis and Computational Study

Mlakić

Selec

Ćaleta

et al. 2023

IJMS

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This study aims to test the inhibition potency of new thienobenzo/naphtho-triazoles toward cholinesterases, evaluate their inhibition selectivity, and interpret the obtained results by molecular modeling. The synthesis of 19 new thienobenzo/naphtho-triazoles by two different approaches resulted in a large group of molecules with different functionalities in the structure. As predicted, most prepared molecules show better inhibition of the enzyme butyrylcholinesterase (BChE), considering that the new molecules were designed according to the previous results. Interestingly, the binding affinity of BChE for even seven new compounds (1, 3, 4, 5, 6, 9, and 13) was similar to that reported for common cholinesterase inhibitors. According to computational study, the active thienobenzo- and naphtho-triazoles are accommodated by cholinesterases through H-bonds involving one of the triazole’s nitrogens, π-π stacking between the aromatic moieties of the ligand and aromatic residues of the active sites of cholinesterases, as well as π-alkyl interactions. For the future design of cholinesterase inhibitors and search for therapeutics for neurological disorders, compounds with a thienobenzo/naphtho-triazole skeleton should be considered.

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MicroRNA regulators of cholinergic signaling link neuromuscular, cardiac and metabolic systems

Abstract: The neurotransmitter acetylcholine (ACh)

Cited by 2 publications

References 49 publications

Design, synthesis and cholinesterase inhibitory properties of new oxazole benzylamine derivatives

Design, synthesis and cholinesterase inhibitory properties of new oxazole benzylamine derivatives

New Thienobenzo/Naphtho-Triazoles as Butyrylcholinesterase Inhibitors: Design, Synthesis and Computational Study

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