In-silico Investigation and Development of Cyclooxygenase-2 (1CX2) Selective Inhibition as a Possible Anti-Inflammatory Activity

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) that specifically target the enzyme cyclooxygenase-2, or COX-2, which causes inflammation and discomfort, are known as COX-2 inhibitors. The objective of this work is to perform the anti-inflammatory activity, and molecular docking studies of compounds. We aim to develop new drug phytochemicals as anti-inflammatory agents targeting COX-2(PDB ID: 1CX2) for treatment. To find potential molecules, the PyRx 0.8 tool has been used to dock 37 potent molecules against COX-2 (PDB ID: 1CX2). The top scorer molecules (phytochemicals) (Dihydromyricetin, Catechin, Chlorogenic acid, Chrysin, and Emodin) were selected. Prior to further analysis, the compounds underwent thorough in vivo evaluation to assess their toxicity and anti-inflammatory properties. The results indicated that dihydromyricetin, catechin, and chlorogenic acid were the sole substances that exhibited both negligible acute toxicity and superior anti-inflammatory properties, surpassing the efficacy of diclofenac sodium, the established medicine. Among the compounds that were evaluated, Dihydromyricetin was shown to possess the most powerful anti-inflammatory properties due to its trihydroxy phenyl chroman-4-one substitution. Correlated to diclofenac (-8.5 Kcal/mol), dihydromyricetin and catechin showed significant bounden affinity, with the lowest binding free energies (-9.9 and -9.2 Kcal/mol) according to the computational study. This correlation between in silico and in vivo studies validated these compound’s powerful anti-inflammatory properties.