Synthesis, In Vivo Anti-Inflammatory Activity, and Molecular Docking Studies of New Isatin Derivatives

Ravi Jarapula,Kiran Gangarapu,Sarangapani Manda,Sriram Rekulapally

doi:10.1155/2016/2181027

Abstract

A novel synthesis of 2-hydroxy-N′-(2-oxoindolin-3-ylidene) benzohydrazide derivatives was synthesized by the condensation of 2-hydroxybenzohydrazide with substituted isatins. The synthesized compounds were characterized by FT-IR, 1H-NMR, and mass spectral data. Further, the compounds were screened for in vivo anti-inflammatory activity by carrageenan induced paw edema method. The tested compounds have shown mild-to-moderate anti-inflammatory activity. The compounds VIIc and VIId exhibited 65% and 63% of paw edema reduction, respectively. The molecular docking studies were also carried out into the active site of COX-1 and COX-2 enzymes (PDB ID: 3N8Y, 3LN1, resp.) using VLife MDS 4.3. The compounds VIIc, VIId, and VIIf exhibited good docking scores of −57.27, −62.02, and −58.18 onto the active site of COX-2 and least dock scores of −8.03, −9.17, and −8.94 on COX-1 enzymes and were comparable with standard COX-2 inhibitor celecoxib. A significant correlation was observed between the in silico and the in vivo studies. The anti-inflammatory and docking results highlight the fact that the synthesized compounds VIIc, VIId, and VIIf could be considered as possible hit as therapeutic agents.

Highlights

Cyclooxygenases (COX) or prostaglandin endoperoxide synthases are the key enzymes in the synthesis of prostaglandins, the main mediators of inflammation, pain, and increased body temperature
The COX-1 is responsible for formation of important biological mediators such as prostanoids, including prostaglandins, prostacyclin, and thromboxane, and involved in pain causing, blood clotting, and protecting the stomach [1], whereas COX-2 is involved in the pain by inflammation and plays a major role in prostaglandin biosynthesis in inflammatory cells and central nervous system [2]
Selective COX-2 inhibitors such as celecoxib and rofecoxib had been developed for ease of inflammation associated with COX [4]

Summary

Introduction

Cyclooxygenases (COX) or prostaglandin endoperoxide synthases are the key enzymes in the synthesis of prostaglandins, the main mediators of inflammation, pain, and increased body temperature (hyperpyrexia). When COX-1 is inhibited, inflammation is reduced, but the protection of the lining of the stomach is lost. This can cause stomach upset as well as ulceration and bleeding from the stomach and even the intestines. Whereas COX-2 is usually specific to inflamed tissue, there is much less gastric irritation associated with COX-2 inhibition together with the decreased risk of peptic ulceration [3]. Selective COX-2 inhibitors such as celecoxib and rofecoxib had been developed for ease of inflammation associated with COX [4]. There is a need for COX-2 inhibitor with no adverse effects

Methods

Results

Conclusion