Dépôt numérique

Arylboronic acids as safe and specific human butyrylcholinesterase inhibitors

Mendes dos Santos, Eduardo; do Amaral e Silva, Nayane Abreu; Gonçalves, Karina Godarth; Vale, André Alvares Marques; de Azevedo-Santos, Ana Paula Silva; Franca, Tanos Celmar Costa; Laplante, Steven ORCID logoORCID: https://orcid.org/0000-0003-2835-5789; Resende, Jackson Antonio Lamounier Camargos; Romeiro, Nelilma Correia; Lima, Josélia Alencar; Martins, Daniela de Luna et Nascimento, Maria do Desterro Soares Brandão (2023). Arylboronic acids as safe and specific human butyrylcholinesterase inhibitors Journal of Molecular Structure , vol. 1290 , nº 135932. pp. 1-14. DOI: 10.1016/j.molstruc.2023.135932.

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The drug treatment of Alzheimer's disease (AD) remains a significant scientific challenge, necessitating a continual search for new drug candidates. In this context, we present here, for the first time, new oxime-arylboronic acid hybrids (L1-L6) as potential anti-AD agents. These hybrids were synthesized and evaluated for their inhibitory capabilities on the activity of non-human cholinesterases [Electrophorus electricus Acetylcholinesterase (EeAChE) and Equine Butyrylcholinesterase (EqBChE)] as well as human cholinesterases [erythrocyte Acetylcholinesterase (hAChE) and plasma Butyrylcholinesterase (hBChE)]. We also assessed the safety of these compounds in a microglia cell line and analyzed the compound-enzyme interactions using molecular docking and molecular dynamics simulations. All compounds were found to be safe for the tests conducted. None of them exhibited significant inhibitory activity against hAChE or EeAChE. However, L1-L5 demonstrated inhibition of EqBChE and hBChE, with L3 being the most potent inhibitor of hBChE (IC50 = 6.41 ± 0.62 µM) and EqBChE (IC50 = 81.28 ± 4.01 µM). Additionally, L2, L3, and L5 showed 8–15 times higher potency as inhibitors of hBChE compared to EqBChE. These findings indicate that the hybrid oxime-arylboronic acids act as specific inhibitors of BChE, with a notable selectivity for hBChE, making them promising structures for the development of more potent and selective hBChE inhibitors. © 2023 Elsevier B.V.

Type de document: Article
Mots-clés libres: Alzheimer's disease; Boronic acids; Butyrylcholinesterase; Human cholinesterases; N9 microglia cell; Organoboron
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 30 déc. 2023 21:54
Dernière modification: 30 déc. 2023 21:54
URI: https://espace.inrs.ca/id/eprint/13654

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