Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 27, Issue 16, Pages 3650-3662Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2019.07.001
Keywords
Acetylcholinesterase; Butyrylcholinesterase; Beta-Amyloid; N-Benzylaniline; Molecular hybridization
Funding
- Department of Health Research (DHR), Ministry of Health and Family Welfare (MHFW), Govt. of India, New Delhi [V25011/215-HRD/2016-HR]
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Novel hybrids N-(4-phenoxybenzyl) aniline were designed, synthesized, and evaluated for their potential AChE inhibitory activity along with antioxidant potential. The inhibitory potential (IC50) of synthesized analogs was evaluated against human cholinesterases (hAChE and hBChE) using Ellman's method. Among all the tested compounds, 42 with trimethoxybenzene substituent showed maximum hAChE inhibition with the competitive type of enzyme inhibition (IC50 = 1.32 mu M; Ki = 0.879 mu M). Further, parallel artificial membrane permeation assay (PAMPA-BBB) showed favorable BBB permeability by most of the synthesized compounds. Meanwhile, compound 42 also inhibited AChE-induced A beta aggregation (39.5-66.9%) in thioflavin T assay. The in vivo behavioral studies showed dose-dependent improvement in learning and memory by compound 42. The ex vivo studies also affirmed the significant AChE inhibition and antioxidant potential of compound 42 in brain homogenates.
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