Molecular docking, synthesis, and antibacterial activity of the analogs of 1-allyl-3-benzoylthiourea.

Background and purpose: The incidence of antibiotic resistance rapidly emerges over the globe. In the present study, the synthesis of thiourea derivatives as antibacterial agents and their biological evaluation are reported.

Experimental approach: Preliminary studies were done by molecular docking of four analogs of 1-allyl-3-benzoylthiourea, clorobiocin, and ciprofloxacin on the DNA gyrase subunit B receptor (PDB: 1KZN). The nucleophilic substitution reaction of benzoyl chloride analogs to the allylthiourea yielded four 1-allyl-3-benzoylthiourea analogs (Cpd 1-4). The reactions were done by a modified Schotten Baumann method. The in vitro antimicrobial activities were determined using the agar dilution method against methicillin-resistant Staphylococcus aureus (MRSA), Salmonella typhi, Escherichia coli, and Pseudomonas aeruginosa.

Findings/results: The in-silico study showed that Cpd 1-4 possesses a good interaction on the DNA gyrase subunit B receptor compared to the ciprofloxacin. Cpd 3 had the best binding affinity with a rerank score of - 91.2304. Although the candidate compounds showed unsatisfactory antibacterial activity, they indicated an increasing trend of growth inhibition along with the increment of concentration. Cpd 1 and 4 exhibited in vitro antibacterial activities against MRSA with a minimum inhibitory concentration value of 1000 µg/mL, better compared to the other compounds.

Conclusion and implication: Despite lacking antibacterial activity, all the synthesized compounds showed an increased trend of growth inhibition along with the increment of concentration. Therefore, additional development should be implemented to the compounds of interest in which optimization of lipophilicity and steric properties are suggested.