No abstract

No abstract

Beta amyloid cleavage enzyme-1 (BACE1) is the key enzyme involved in Aβ peptide formation in Alzheimer's disease pathogenesis. We intend to target this enzyme by exploring benzimidazole analogues against BACE1 as potential anti-Alzheimer agents. Docking studies were performed to determine the hydrogen bond interactions between the designed molecules and the target protein's active site. Research indicates the relationship between oxidative stress and Aβ effect in precipitating neurodegeneration; hence, the series was also studied in vitro to ascertain its neuroprotective role by performing the lipid peroxidation assay. In silico absorption, distribution, metabolism, and excretion studies were undertaken to assess the drug-like suitability of the analogues. To judge the effect of the synthesized analogues on central nervous system (CNS), toxicity and memory model studies were conducted on mice. Thus, overall results showcase analogues 11 and 14 as the most promising ones with the dual role of BACE1 inhibition and neuroprotection, along with memory retention. K E Y W O R D SBACE1, docking, in silico ADME studies, in vitro LPO assay, memory model studies, toxicity study

BACE1 plays critical role in the formation of neurotoxic β-amyloid (Aβ) peptides in brain and so is regarded as an ideal drug design target for Alzheimer's disease. With this perspective, we have designed BACE1 inhibitors, specifically substituted aryl ureido analogues. Docking studies revealed interactions with the crucial catalytic Aspartate dyad of BACE1 enzyme. In silico ADME studies predicted favourable drug like properties for these analogues. Molecular docking results were in consensus with the pharmacological screening of the synthesized analogues. Overall results indicate that analogue 4c and 4d exhibit equivalent BACE1 enzyme inhibition.