Design, Synthesis, Biological Evaluation and Docking Studies of Some New Diclofenac Analogues

Abstract

There is still a need for new, selective COX-2 inhibitors with an improved safety profile, therefore, a series of diclofenac analogs were designed and different physicochem. properties were calcd. such as log P, hydrogen donor, hydrogen-acceptor, mol. wt. and pKa etc. and compared with diclofenac and study was aimed to design and calc. different physicochem. properties and attempt to introduce diclofenac derivs. with improved anti-inflammatory profile along with docking focusing on COX-2. Carrageenan-induced paw edema to evaluate the anti-inflammatory activity of the conjugates 4 groups (n = 6) of Wistar rats (150-200 g) were examd. A first group of rats was used as a control without using the drug, group II received Diclofenac 20 mg kg-1, received PEG600-Diclo conjugate and PEG4000-Diclo conjugate (52.60 mg kg-1 and 214 mg kg-1 resp.), where the dose was molecularly equiv. to the diclofenac. Result showed a significant (p<0.05) dose dependent increase in reaction time in mice in the method at the doses of 150 and 200 mg/kg body wt. Also docking studies specifically on COX-2 exhibited promising anti-inflammatory effect as demonstrated by statistically significant (p<0.05) inhibition of paw vol. at the dose of 150 mg/kg body wt. and the dose of 500 mg/kg body wt. at the three hours of study. In this study mol. docking results, along with biol. assay data, show that all compds. have a potential anti-inflammatory activity comparable to diclofenac. [on SciFinder(R)]