| Summary: | In search of potent anti-Alzheimer agent benzimidazole based Schiff base derivatives (1–18) were synthesized and evaluated as dual inhibitor for acetylcholinesterase and butyrylcholinesterase enzymes. All analogs among the series except analog 1 and 16 showed a variable degree of inhibitory activity with IC50 value ranging between 0.10 ± 0.01 to 12.40 ± 0.30 µM for acetylcholinesterase and 0.20 ± 0.01 to 11.10 ± 0.30 µM for butyrylcholinesterase. The most potent analog found among the series was analog 8 having IC50 value 0.10 ± 0.01 and 0.20 ± 0.01 µM for both acetylcholinesterase and butyrylcholinesterase inhibition respectively. The structures of all synthesized analogs were confirmed through NMR and HR-EIMS. Structure activity relationship (SAR) has been established for all newly synthesized derivatives. To understand the binding interaction of most active derivatives with enzyme active site, molecular docking study were performed. The toxicity and mutagenicity of compound 8 was predicted using in silico software, namely Derek Nexus® (version 6.3). Various toxicity endpoints, including chromosomal damage, skin sensitization, hepatotoxicity were predicted. The degradation profile of compound 8 was predicted in silico by Zeneth software (version 9.0.1) resulting in a probability of the formation of seven potential degradation products. © 2024 Elsevier B.V.
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