Synthesis and Pain inhibition activity of the analogs of 1-allyl-3-benzoylthiourea for new analgesic lead compound discovery

Objective: The study aimed to synthesize four analogs of 1-allyl-3-ben-zoylthiourea (R= H; 2-Cl; 3-Cl; and 4-Cl), and evaluate their pain inhibition activities. Method: The chemical structure was drawn assisted by ChemDraw Ultra 8.0 and Chem3D Ultra 8.0 software. Molegro Virtual Docker 5.0 software was utilized for the docking process, to determine the interaction energy values between compounds of interest and the COX-2 receptor (PDB: 1PXX). The synthesis step was done by nucleophilic substitution (benzoylation) on allylthiourea compound via modified Schotten-Baumann reaction. Chemical structure analysis was evaluated by means of Infra-Red, Nuclear Magnetic Resonance, and Mass Spectroscopy methods. The pain inhibition assay was done using acetic acid induced writhing test, using mice (Mus musculus) as animal model. Results: Preliminary in silico screening showed that all four candidate compounds possessed good interaction on COX-2 receptor. The synthesis process produced rendemen of the compounds vary between 15.2 %-47%. Chemical structure evaluation confirmed the structural match of the products as expected. Acetic acid induced writhing test in mice (Mus musculus) showed that three compounds possessed a better pain inhibition activity compared to positive control diclofenac sodium. Conclusion: 1-allyl-3-benzoylthiourea analogs showed good pain inhibition activity.The compounds can serve as leads for analgesic activity through the inhibition of COX-2.