Synthesis, Analgesic Evaluation, Molecular Docking and DFT Studies of Novel 4-Aminoantipyrine Derivatives

Abstract

The present study investigates the analgesic efficacy of four newly synthesized 4-aminoantipyrine derivatives (4a-4d), which were obtained by conjugating 4-aminoantipyrine with oxadiazole and triazole moieties. The derivatives were evaluated for their analgesic properties using the writhing method in Swiss albino mice, revealing that compound 4c exhibited the highest activity (69%), comparable to paracetamol (71%). The remaining derivatives displayed varying degrees of analgesic activity. Molecular docking studies using MOE software demonstrated significant binding affinities of the derivatives to both mu-opioid (5C1M) and kappa-opioid (6B73) receptors, with compound 4c showing the strongest interactions. DFT calculations, performed with the Gaussian program, provided insights into the electronic structure and stability of the compounds, indicating their potential as effective analgesic agents. The study underscores the promise of these derivatives, particularly compound 4c, for further development in the field of analgesic drug discovery.