Anti-inflammatory, Anti-thrombotic and Molecular Docking Studies of 1,3,4 Oxadiazole Derivatives in Rats

Abstract

Background: 1,3,4-Oxadiazole have been reported for the diverse use in medicine because of its versatile pharmacological properties. In continuation of our on-going research the present study is established to investigate the in-vitro and in-vivo anti-inflammatory activity of 5-{[2-(4-chlorophenoxy)propan-2-yl]-1,3,4-oxadiazole-2-thiol (1) and its derivatives N-substituted 5-{[2-(4-chlorophenoxy)propan-2-yl]-1,3,4-oxadiazol-2ylthio} acetamides (3a-3i). Methods: In-vitro and in-vivo anti-inflammatory activity was evaluated by albumin protein denaturation method and carrageenan-induced edema respectively. Ligands 1, standard, and 3a-3h were docked with COX-2 (3LN1) by Patch Dock to find the docking transformations. All the values are expressed in mean ± SEM. Statistical significance was calculated by one way ANOVA with Dennett’s test. Results: Experimental results for in-vitro and in-vivo anti-inflammatory activity suggested that 3a and 3c as potent anti-inflammatory compounds. Moreover, in the in-vivo rat model, the compound 3h and 3a showed a significant role in enhancing clotting time. In silico study of tested compounds showed that all these compounds except 1 and 3e show higher docking score than standard drug diclofenac sodium. In addition, impressive inhibitory potential against COX-2 was observed with higher docking scores (5172-5938) with Atomic Contact Energy (ACE) values (-143.21 to -380.56 kcal/mol) than the standard diclofenac sodium (Docking score 4612; ACE -242.58 kcal/mol). Conclusion: All the results suggest that these compounds may be used in the development of anti-inflammatory pharmaceutical products.