Study Study In Silico, Synthesis and Analgesic Activity Test of N-Benzoyl-N'-4-Methoxyphenylthiourea Compound in Mus musculus

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Abstract

Pain is an unpleasant sensory and emotional experience resulting from actual or potential tissue damage and is the most common reason individuals seek health care. Nonsteroidal anti-inflammatory drugs (NSAIDs), which act through cyclooxygenase inhibition, provide good analgesic effects but carry a risk of gastrointestinal toxicity. This study aimed to develop a thiourea derivative compound, namely N-benzoyl-N'-4-methoxyphenylthiourea (MFT), as an alternative analgesic candidate with lower side effects. The research stages included silico testing, synthesis, structure confirmation, and in vivo analgesic activity testing. In silico testing was performed by molecular docking using the Molecular Operating Environment (MOE) program against the COX-2 receptor (PDB code 5IKR), validated through redocking (RMSD 0.135-0.136 Å). Synthesis was carried out via the Schotten-Baumann reaction between 4-methoxyphenylthiourea and benzoyl chloride, yielding the MFT compound with a yield of 34.80%, single-spot purity on TLC testing, and a consistent melting point of 171-173°C. Structure confirmation using UV, IR, 1H-NMR, 13C-NMR, and GC-MS spectrophotometry showed that the synthesized compound matched the target structure. In vivo analgesic activity testing in mice (Mus musculus) using the writhing method showed that at a dose of 25 mg/kgBW, the analgesic activity of MFT was not significantly different from mefenamic acid (p>0.05), whereas at a dose of 100 mg/kgBW the two differed significantly (p<0.05). The N-benzoyl-N'-4-methoxyphenylthiourea compound has potential to be developed as a new analgesic drug candidate.