Synthesis and molecular docking of thiourea derivatives as antibacterial agents targeting enzymes involved in biosynthesis of bacterial cell wall

Background: New antibacterials are needed due to the increasing resistance of bacteria to existing antibiotics. Thiourea derivative compounds (benzoylthiourea and 1,3-dibenzoylthiourea) contain aromatic groups, thio groups (C=S), and amide groups (H2N-C=O), which are commonly found in the class of antibacterial drugs. Molecular docking can be used to predict their antibacterial activity. Objective: This study aimed to synthesise thiourea derivatives and predict their antibacterial activity by in silico method. Methods: Synthesis was performed using nucleophilic substitution reactions. The synthesised compounds were identified using UV-Vis, FT-IR, and H-1-NMR. Molecular docking was conducted using the MOE program ver 2022.02. Results: Benzoylthiourea (BTU) and 1,3-dibenzoylthiourea (DBTU) compounds were obtained with yields of 36.55% and 12.68%, respectively. The melting point 171-173 degrees C for BTU and 202-204 degrees C for DBTU. Molecular docking results showed higher binding affinity of DBTU against PBP2a (docking score < -5.75 kcal/mol) and FaBH (docking score <-4.7935 kcal/mol) compared to the corresponding native ligands, while the two compounds had lower affinity for the muramyl ligase. Conclusion: BTU and DBTU can be synthesised by nucleophilic substitution reactions. DBTU is predicted to exhibit antibacterial activity against Methicilin Resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis.