AZOMETHINES, ISOXAZOLE, N-SUBSTITUTED PYRAZOLES AND PYRIMIDINE RING CONTAINING CURCUMIN DERIVATIVES

Mahmood Ahmed, Muhammad Abdul Qadir and Muhammad Muddassar

Department of Chemistry, University of the Punjab, Lahore, Pakistan

Abstract

Curcumin has shown large number of pharmacological properties against different phenotypes of various disease models. Different synthetic routes have been employed to develop its various derivatives for diverse biological functions. In this study, curcumin derived azomethine, isoxazole, pyrimidines and N-substituted pyrazoles were synthesized to investigate their urease enzyme inhibition. The structures of newly synthesized compounds were described by IR, 1H NMR and 13C NMR spectral data. Urease enzyme inhibition was evaluated through in vitro assays and inhibition assays result revealed that thiourea conjugated curcumin was found to be more potent (IC50 = 2.44±0.07 μM) among the tested compounds. The compounds with diazine ring system showed better urease inhibition (IC50 = 11.43±0.21-19.63±0.28 μM) than the standard urease inhibitor thiourea (IC50 = 22.61±0.23 μM). Kinetic data revealed that these compounds were competitive inhibitors with Ki values 20.0, 19.87, 20.23 and 19.11 μM respectively. Molecular docking studies were also performed to identify the plausible binding mode of the most active compounds.

Keywords: Schiff bases, urease inhibition, kinetic studies, curcumin.