Pharmacophore mapping and docking studies were carried out to develop optimized leads for the design of 1,4-dihydropyridines as acetylcholinesterase inhibitors. Theoretical ADME analysis was also carried out. Based on correlating results, selective 1,4-dihydropyridines were synthesized by a novel green catalyst based approach. Structures and purity of newly synthesized compounds were confirmed by using LCMS and NMR. Biological evaluation of these molecules showed 5 compounds to be potent acetylcholinesterase inhibitors with IC(50) (hAChE) in the nanomolar range. Molecular modeling investigation supports dual AChE inhibitory profile for all the compounds, binding simultaneously at the catalytic active and at peripheral anionic sites of the enzyme. These compounds are being carried forward as promising leads in the treatment of Alzheimer's disease.

Design, synthesis, and evaluation of selected 1,4-dihydropyridine type acetylcholinesterase inhibitors

245th National Meeting (2013)

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