Abstract

A series of 3-substituted-4-hydroxy-2-oxo-1-phenyl/methylquinolin-2-(1H)-one derivatives were synthesized by condensation of two moles of 3-acetyl-4-hydroxy-1-phenyl/methyl quinolin-2(1H)-one with ketone by Claisen-Schmidt reaction resulted in 3-substituted-4-hydroxy-2-oxo-1-phenyl/methylquinolin-2-(1H)-one derivatives {(III a/b 1-5)}. All the synthesized compounds were characterized by IR and NMR data and analgesic activity was ascertained by Eddy’s hot plate method. The newly synthesized compounds showed satisfactory efficacy when compared to the reference standard drug Ibuprofen. Compounds (III b-1, III b-2, III b-3) showed maximal analgesic effect after 1 h and waned off after 4 h. Using Molegro Virtual Docker (MVD-2013, 6.0) software, docking studies of the title compounds {IIIa/b-(1-5)} were carried out. The synthesized compounds exhibited well-conserved hydrogen bonds with one or more amino acid residues in the active pocket of the Human GRIK1 domain (PDB ID: 4MF3). The interpretation of docking studies revealed that the MolDock Score of compound (III b-1) was (-137.967), which is comparable to that of the standard ligand (-138.637) and standard drug Ibuprofen (-139.385) and (III b-1) showed promising analgesic activity.

Key words: Analgesic, docking; Claisen-Schmidt; Eddy’s hot plate; Moldock; Quinolin-2-one