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, hydrogenacceptor, 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 antiinflammatory 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.