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

Abstract

Aim: There is still a need for new, selective COX-2 inhibitors with an improved safety profile, therefore, a series of diclofenac analogues were designed and different physicochemical properties were calculated such as log P, hydrogen donor, hydrogen-acceptor, molecular weight and pKa etc and compared with diclofenac and study was aimed to design and calculate different physicochemical properties and attempt to introduce diclofenac derivatives with improved anti-inflammatory profile along with docking focusingon CO X-2. Materials and Method: Carrageenan-induced paw edema to evaluate the anti-inflammatory activity of the conjugates 4 groups (n = 6) of Wistar rats (150–200 g) were examined. 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 respectively), where the dose was molecularly equivalent to the diclofenac. Results: 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 weight. Also docking studies specifically on COX-2 exhibited promising anti-inflammatory effect as demonstrated by statistically significant (p<0.05) inhibition of paw volume at the dose of 150 mg/kg body weight and the dose of 500 mg/kg body weight at the three hours of study. Conclusion: In this study molecular docking results, along with biological assay data, show that all compounds have a potential anti-inflammatory activity comparable to diclofenac.