TY - JOUR
T1 - Identification and evaluation of boronic compounds ameliorating cognitive deficit in orchiectomized rats
AU - Farfán-García, Eunice D.
AU - Rosales-Hernández, Martha C.
AU - Castillo-García, Emily L.
AU - Abad-García, Antonio
AU - Ruiz-Maciel, Omar
AU - Velasco-Silveyra, Luz M.
AU - González-Muñiz, Alejandra Y.
AU - Andrade-Jorge, Erik
AU - Soriano-Ursúa, Marvin A.
N1 - Publisher Copyright:
© 2022 Elsevier GmbH
PY - 2022/7
Y1 - 2022/7
N2 - Background: Boron is a trace element with increasing importance in drug design. In this sense, boronic acids are emerging as therapeutic agents for several diseases. Methods: Herein, 3- and 4- acetamidophenylboronic acids and 4-acetamidophenylboronic acid pinacol ester were identified as potential inhibitors of acetylcholinesterase through docking assays on eel, rat, and human acetylcholinesterases indicating binding on the gorge region of the target enzymes. Then, these compounds were evaluated in vitro and in vivo. Results: It was found these compounds showed ability to inhibit acetylcholinesterase as competitive and non-competitive inhibitors. But also, these compounds were non-toxic to PC12 cells at micromolar concentration, and they have the ability to protect those cells against damage by amyloid-beta. Conclusions: Noticeably, intraperitoneal administration of these boronic compounds to rats with the cognitive deficit induced by orchiectomy provided ameliorative effects on disrupted behavior and neuronal damage induced by hormonal deprivation. Additional approaches are required to evaluate the possibility of multiple mechanisms of action for the observed effects in the central nervous system.
AB - Background: Boron is a trace element with increasing importance in drug design. In this sense, boronic acids are emerging as therapeutic agents for several diseases. Methods: Herein, 3- and 4- acetamidophenylboronic acids and 4-acetamidophenylboronic acid pinacol ester were identified as potential inhibitors of acetylcholinesterase through docking assays on eel, rat, and human acetylcholinesterases indicating binding on the gorge region of the target enzymes. Then, these compounds were evaluated in vitro and in vivo. Results: It was found these compounds showed ability to inhibit acetylcholinesterase as competitive and non-competitive inhibitors. But also, these compounds were non-toxic to PC12 cells at micromolar concentration, and they have the ability to protect those cells against damage by amyloid-beta. Conclusions: Noticeably, intraperitoneal administration of these boronic compounds to rats with the cognitive deficit induced by orchiectomy provided ameliorative effects on disrupted behavior and neuronal damage induced by hormonal deprivation. Additional approaches are required to evaluate the possibility of multiple mechanisms of action for the observed effects in the central nervous system.
KW - Acetylcholinesterase
KW - Alzheimer disease
KW - Amyloid
KW - Boron
KW - Boronic acids
KW - Cognitive deficit
UR - http://www.scopus.com/inward/record.url?scp=85127090605&partnerID=8YFLogxK
U2 - 10.1016/j.jtemb.2022.126979
DO - 10.1016/j.jtemb.2022.126979
M3 - Artículo
C2 - 35364473
AN - SCOPUS:85127090605
SN - 0946-672X
VL - 72
JO - Journal of Trace Elements in Medicine and Biology
JF - Journal of Trace Elements in Medicine and Biology
M1 - 126979
ER -