SYNTHESIS, IN-VIVO ANTI-INFLAMMATORY EVALUATION AND MOLECULAR DOCKING STUDY OF A SERIES OF SUBSTITUTED XANTHONE DERIVATIVES AS NOVEL COX-2 INHIBITORS

A series of 3,6-bis (3^/-substituted propoxy) and 3,6-bis (5^/-substituted pentyloxy) xanthone derivatives was synthesized by the condensation of 3,6-bis (3^/– bromopropoxy) and 3,6-bis (5^/–bromopentyloxy) xanthones with primary or secondary amines. These compounds were characterized by FT-IR, ¹H NMR, and Mass spectral data. The anti-inflammatory study of the synthesized compounds was carried out using the carrageenan-induced rat paw edema method on Albino rats of Wistar strains. Thirty minutes after injection of 1% carrageenan solution into the sub plantar surface of the left hind paw, synthesized drugs were orally administered at a dose of 100 &200 mg/kg body weight. The compounds S3, S17, and S20 at a dose of 200 mg/kg body weight showed 63.32%,62.75%, and 60.71% paw edema reduction respectively after 6 hours as compared to standard diclofenac (10mg/kg) body weight which showed 68.27% reduction of paw edema after 6 hours. The molecular docking studies were also carried out in the active site of COX-2 enzymes (PDB ID: 1CX2) using Discovery studio version 2.5. The in-silico ligand binding interactions of compounds S3_, S6_, S14_, S17, and S20 suggested approx.> 30% higher binding energy values than the standard Diclofenac (Binding energy -155.46 Kcal/mol). A significant correlation was observed between the in-silico and the in-vivo studies of the synthesized compounds. With the help of anti-inflammatory and docking, the synthesized compounds S3_, S17, and S20 could be considered as possible hits as anti-inflammatory agents.