Studi Penambatan Molekuler dan Uji Aktivitas Analgesik Senyawa (E)-1- morfolino-3-fenilprop-2-en-1-on secara In Vivo dengan Metode Writhing Test

Abstract

Pain is an unpleasant sensory and emotional experience associated with, or resembling, actual or potential tissue damage. Long-term use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as sodium diclofenac may lead to adverse effects, including myocardial infarction, stroke, bleeding, and kidney damage. NSAIDs work by inhibiting the cyclooxygenase (COX) enzyme, which plays a role in the production of prostaglandins that cause pain and inflammation. Therefore, more effective analgesics with minimal side effects are needed. One of the natural compounds with analgesic properties is cinnamic acid and its derivative, (E)-1-morfolino-3-phenylprop-2-en-1-one (compound 3a). This study aimed to evaluate the anti-inflammatory activity of compound 3a through the in vivo writhing test and molecular docking studies. The writhing test was performed on Balb/c mice, administering compound 3a at doses of 10 mg/kg, 20 mg/kg, and 40 mg/kg, with sodium diclofenac as the positive control. Molecular docking was carried out using AutoDock Vina in PyRx software, docking compound 3a to COX-2 (PDB ID: 1PXX) and COX-1 (PDB ID: 1EQG) receptors. The results showed that compound 3a exhibited the best analgesic activity at a dose of 40 mg/kg, with a %protective value of 52,48%. The molecular docking results showed that compound 3a had good binding affinity for both COX-2 and COX-1, with binding affinities of -8,1 kcal/mol for COX-2 and -7,8 kcal/mol for COX-1, higher than diclofenac (-8,6 kcal/mol for COX-2 and -8,4 kcal/mol for COX-1). The interactions showed a tendency for better affinity with COX-2 (PDB ID: 1PXX). Diclofenac remains superior in terms of bond stability, making it more effective in binding to both target enzymes. However, compound 3a still shows good potential as a COX-2 inhibitor, which requires further testing in drug development.