DESIGN, SYNTHESIS, CHARACTERIZATION AND EVALUATION OF NEWER POTENT APOLIPOPROTEIN E4 INHIBITORS FOR THE TREATMENT OF ALZHEIMER’S DISEASEAbstract
A major genetic suspect for Alzheimer’s disease is the pathological conformation assumed by Apolipoprotein E4(Apo E4) through intramolecular interaction. The aim of the current study is to synthesize newer potent Apo E4 inhibitors. In the present study, with specific pharmacophoric features of three Hydrogen bond donors and three hydrophobic spheres, a large library of ligands was constructed for Apo E4 inhibitors. The newly designed ligands were subjected for docking studies using Autodock®Tools 1.5.6 and optimized for Lipinski rule of five and further screened by in-silico toxicity studies. Out of that oxazole heterocyclic nucleus and its analogs were chosen for synthesis and characterized for spectral analysis such as IR, NMR, LC-MS. The active compound LS 4 was evaluated for cytotoxicity study through MTT Assay and neuroprotective study against Aβ- L-DOPA toxicity induced SH-5YSY cell line. Compound LS 4 showed 93.81% of neuroprotective activity at 1.567μg/ml.
R. Priyadarsini * and P. L. Kumar
Department of Pharmaceutical Chemistry, Madras Medical College, Chennai, Tamil Nadu, India.
09 September 2019
26 January 2021
18 February 2021
01 March 2021