Design and Synthesis of Some New AChEIs as Anti-Alzheimer Agents. Neurodegenerative Disorder

      Аннотация: A new series of isoindoline-1,3-dione derivatives were synthesized by using 2-(3-bromopropyl)isoindoline-1,3-dione and phenoxy acetic acids or quinoline. The reaction was monitored by TLC using suitable mobile phase and also determined the melting point and other characterization like IR, 1H NMR, 13C NMR and Mass spectral analysis. When designing new molecules as anti-alzheimer agents, first we carried out in silico study in which isoindoline containing reference molecules as well as active site containing ligand (Donepezil) were docked using PDB 1EVE, Acetylcholinesterase enzyme, the docking study suggested interaction with PAS and CAS is essential for anti- alzheimer activity. Then we docked new molecules, they showed same interaction as that of reference molecules. Based upon docking study molecules were synthesized and screened for in vitro anti-alzheimer activity by using Ellman assay. The Compound (7a) showed good anti-Alzheimer activity with IC50 = 32nM. In docking study as well as in vitro study we found compound 7a as promising anti-alzheimer agent. Based upon the results we conclude that these molecules can act as good anti- alzheimer agents.

Ключевые слова: Isoindoline-1, 3-dione, Quinoline, Ellman Assay, Anti-Alzheimer activity