Synthesis, biological evaluation, molecular dynamic and docking study of benzimidazole analogues as potent acetylcholinesterase and butyrylcholinesterase inhibitors
摘要
Benzimidazole analogues (1–15) were prepared and screened for in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition. All analogues showed concentration-dependent inhibition with IC50 values ranging between 0.20 ± 0.01 and 8.10 ± 0.30 µM against acetylcholinesterase and 0.10 ± 0.01 to 8.20 ± 0.30 µM against butyrylcholinesterase by comparing with the standard drug donepezil having IC50 = 0.016 ± 0.001 µM and 0.30 ± 0.010 µM for AChE and BuChE respectively. Analogue 7 (IC50 = 0.20 ± 0.01 µM and 0.10 ± 0.010 µM) and compound 9 (IC50 = 0.40 ± 0.01 µM and 0.10 ± 0.010 µM) for AChE and BuChE respectively were found most potent inhibitor for both enzymes. Both compounds having trifluoromethyl group at para and ortho location of the ring respectively. Furthermore, the analogues were characterized by NMR-spectroscopy, and Mass-spectrometry (HR-MS). The molecular docking studies were directed, to study the binding interface among the most active analogues and the active site of the enzyme.