Synthesis and Pain Inhibition Activity of the Analogs of 1-Allyl-3-Benzoylthiourea for New Analgesic Lead Compound Discovery

Abstract

Objective: The study aimed to synthesize four analogs of 1-allyl-3-benzoylthiourea (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.Keywords: Synthesis; 1-allyl-3-benzoylthiourea; COX-2; Analgesic; Lead Compound; Key Message: Thiourea compounds have been known for their vary pharmacological activites. The novelty of this research is the compounds that are synthesized in search of analgesic lead compound. Additionally, the results showed that the compounds possessed good pain inhibition activity, and need to be developed further.

Exploring the latest trends in chemistry, structure, coordination, and diverse applications of 1-acyl-3-substituted thioureas: a comprehensive review

“…Only (100a) and (100d) showed comparatively better activity against S. aureus with a MIC value of 1000 mg mL −1 . 100 Carbamothioylfuran-2-carboxamide derivatives (101a-f) were investigated against bacterial strains (S. aureus, E. coli, and B. cereus). Compound (101f) showed antibacterial activity against all the tested strains with MIC values in the range of 230-295 mg mL −1 , whereas derivatives (101a, 101b and 101c) exhibited activity against two bacterial strains E. coli and B. cereus with MIC values in the range of 240-280 mg mL −1 .…”

New N-acyl Thiourea Derivatives: Synthesis, Standardized Quantification Method and In Vitro Evaluation of Potential Biological Activities

“…Thiourea derivatives have been reported in the literature for their multiple biological activities, including antibacterial [1][2][3][4], antifungal [5,6], antitubercular [7][8][9], anthelmintic [10], antiviral [11,12], anticancer [4,13,14], analgesic [15][16][17], anti-inflammatory [1,18], anti-diabetic [19,20], anticonvulsant [21], antithyroid [22,23], antioxidant [24], insecticidal [25], herbicidal [26], and rodenticidal [27] effects. Thiourea derivatives are also versatile intermediates for the synthesis of heterocyclic compounds such as 1,3-thiazoles, pyrimidines, 1,2,4-triazines and 1,3-quinazolines [28].…”