TY - JOUR
T1 - Identification of two arylimides as cholinesterase inhibitors and testing of propranolol addition on impaired rat memory
AU - Ciprés-Flores, Fabiola J.
AU - Farfán-García, Eunice D.
AU - Andrade-Jorge, Erik
AU - Cuevas-Hernández, Roberto I.
AU - Tamay-Cach, Feliciano
AU - Martínez-Archundia, Marlet
AU - Trujillo-Ferrara, José G.
AU - Soriano-Ursúa, Marvin A.
N1 - Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Alzheimer's disease (AD) is clearly linked to the decline of acetylcholine (ACh) effects in the brain. These effects are regulated by the hydrolytic action of acetylcholinesterase (AChE). Therefore, a central palliative treatment of AD is the administration of AChE inhibitors although additional mechanisms are currently described and tested for generating advantageous therapeutic strategies. In this work, we tested new arylamides and arylimides as potential inhibitors of AChE using in silico tools. Then, these compounds were tested in vitro, and two selected compounds, C7 and C8, as well as propranolol showed inhibition of AChE. In addition, they demonstrated an advantageous acute toxicity profile compared to that of galantamine as a reference AChE inhibitor. in vivo evaluation of memory performance enhancement was performed in an animal model of cognitive disturbance with each of these compounds and propranolol individually as well as each compound combined with propranolol. Memory improvement was observed in each case, but without a significant additive effect with the combinations.
AB - Alzheimer's disease (AD) is clearly linked to the decline of acetylcholine (ACh) effects in the brain. These effects are regulated by the hydrolytic action of acetylcholinesterase (AChE). Therefore, a central palliative treatment of AD is the administration of AChE inhibitors although additional mechanisms are currently described and tested for generating advantageous therapeutic strategies. In this work, we tested new arylamides and arylimides as potential inhibitors of AChE using in silico tools. Then, these compounds were tested in vitro, and two selected compounds, C7 and C8, as well as propranolol showed inhibition of AChE. In addition, they demonstrated an advantageous acute toxicity profile compared to that of galantamine as a reference AChE inhibitor. in vivo evaluation of memory performance enhancement was performed in an animal model of cognitive disturbance with each of these compounds and propranolol individually as well as each compound combined with propranolol. Memory improvement was observed in each case, but without a significant additive effect with the combinations.
KW - Alzheimer's disease
KW - arylimides
KW - beta-blockers
KW - cholinesterase inhibitors
KW - combination therapy
KW - docking
KW - hormone deprivation
UR - http://www.scopus.com/inward/record.url?scp=85076924038&partnerID=8YFLogxK
U2 - 10.1002/ddr.21633
DO - 10.1002/ddr.21633
M3 - Artículo
C2 - 31875337
AN - SCOPUS:85076924038
SN - 0272-4391
VL - 81
SP - 256
EP - 266
JO - Drug Development Research
JF - Drug Development Research
IS - 2
ER -