Pharmacological Evaluation of Neuroprotective Activity of Newly Synthesized Drug Candidates in Alzheimer’s Disease Models

Abstract

The symptoms of Alzheimer's disease (AD), a neurodegenerative disease that worsens over time, include oxidative stress, neuronal death, and failure of the cholinergic system. The present investigation set out to evaluate, in Alzheimer's disease animal models, the neuroprotective efficacy of novel drug candidates. Five newly synthesised medicines (NSD-1 through NSD-5) were tested for their acetylcholinesterase (AChE) inhibitory activity and neuroprotective effectiveness. We picked NSD-3 for in vivo testing in 8 groups of Wistar rats with scopolamine-induced Alzheimer's disease models because it was the most promising choice. Ability to think critically was assessed using the Morris Water Maze and the Y-Maze. Among the biochemical measurements that were taken were the levels of catalase, superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione (GSH), and activity of AChE in the brain. Furthermore, histological examinations of hippocampal tissues were also performed.In terms of AChE inhibitory efficacy, NSD-3 demonstrated the highest level at 0.82 ± 0.06 μM. Treatment with NSD-3 (20 mg/kg) significantly improved memory recall and reduced escape latency in the disease control group from 58.4 ± 4.2 s to 24.7 ± 2.8 s (p < 0.001). With a p-value less than 0.001, the proportion of spontaneous alternation behaviour increased from 42.3 ± 3.5% to 71.8 ± 4.1%. Brain AChE activity decreased by 48.6%, while MDA levels decreased from 5.84 ± 0.43 to 2.71 ± 0.28 nmol/mg protein. A significant rise was observed in the levels of GSH to 8.12 ± 0.56 μmol/g tissue, SOD to 18.7 ± 1.4 U/mg protein, and catalase to 31.5 ± 2.3 U/mg protein. Histopathological analysis revealed a remarkable reduction in neurodegenerative changes and a considerable preservation of hippocampus neurones in treated AD rats compared to untreated AD rats.Notable neuroprotective characteristics were exhibited by the newly synthesised chemical NSD-3 through acetylcholinesterase inhibition, antioxidant activity, and preservation of neural architecture. These findings suggest that NSD-3 may hold promise as a lead compound in the development of novel therapies for Alzheimer's disease.