Environmental Toxin Induced BACE1 Gene Expression: Selective Inhibition By N-Methyl Piperidinone Analogues Of Curcumin

Abstract

A series of 1-Methyl-3, 5-bis-(heteroaryl methylene)-piperidin-4-one was synthesised and characterised. Scaffold hoping was performed using in silico tools on N-Methyl piperidinone core structure by substitution at terminal position with six different heterocyclic rings. Combination of ligand-based drug design (LBDD) and structure-based drug design (SBDD) methodology is used for identifying the lead molecule. The hit molecule identified (PM6) was subjected to docking against beta-site amyloid precursor protein cleaving enzyme 1(PDB ID-3IN3). The in vitro MTT assay was conducted for compound code PM6 using neuroblastoma cells. The same experiment was performed against standard drug curcumin. The compound code PM6 exhibited more neuroprotective action on neuroblastoma cells treated with Beta amyloid(10µM) compared to curcumin. Further, the in vitro results are in good correlation with the in silico study conducted.