Identification of two arylimides as cholinesterase inhibitors and testing of propranolol addition on impaired rat memory

Abstract

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.

Synthesis, In Silico, and Biological Evaluation of a Borinic Tryptophan-Derivative That Induces Melatonin-like Amelioration of Cognitive Deficit in Male Rat

“…The diminished cognitive performance in passive avoidance task (PAT) was observed after three weeks of orchiectomy as reported elsewhere [ 34 ]. Thus, a significant decrease in latency into the safe compartment was registered in comparison with homogeneous pre-surgical gonadectomy behavior.…”

“…The resulting complexes were visualized using VMD version 1.9.3 software, University of Illinois at Urbana-Champaign, Champaign, IL, USA [ 64 ]. The free energy and Ki values yielded from the Autodock program were considered for estimating affinity values as elsewhere [ 34 ].…”

“…The open field test was conducted for 5 min prior to treatments and memory evaluation to discard any motor disturbance affecting performance. In brief, rats were placed into motor activity measuring cages (50 cm × 50 cm × 50 cm, with detectors each 2.5 cm, OA-BioMed OMNIALVA ® , Mexico City, Mexico) for determining total number of movements, distance traveled, highest speed, and vertical movements as elsewhere [ 34 ]. Treatment were in a similar posology to those reported as active in rat memory evaluation [ 66 , 67 ].…”

“…For evaluating memory, the passive avoidance test (PAT) was performed for each group as reported previously [ 34 , 54 ]. In brief, we used an apparatus (OMNIALVA ® , Mexico City, México) with two compartments, including the safe (white) and the shock (black) compartments.…”

Alzheimer's disease: A need for personalized therapeutic approaches

“…Different therapeutic approaches such as an inhibition of the degradation of acetylcholine (ACh) by inhibiting acetylcholine esterase (AChE) is currently used in patients to reduce disease symptoms without clear effect on disease progression (Wilkinson, Francis, Schwam, & Payne‐Parrish, 2004). Three papers in this issue report different approaches to develop a new AChE inhibitor (Carreiras et al 2020; Chakravarty, Ju, Chen, & Tam, 2019; Ciprés‐Flores et al, 2019). ACh can signal either through different nicotinic receptors or muscarinic receptors.…”