Synthesis of urea and thiourea derivatives bearing 1,2,4-oxadiazole ring and evaluation of their antimicrobial activities

Urea, thiourea and 1,2,4-oxadiazol compounds, are of great interest due to their different activities such as anti-inflammatory, antiviral, analgesic, fungicidal, herbicidal, diuretic, antihelminthic and antitumor along with antimicrobial activities. In this research, it was aimed to investigate the synthesis and antimicrobial activities of new compounds, which are believed to have significant biological activity by combining urea, thiourea and oxadiazole pharmacophores. In the first step, 5-chloromethyl-3-aryl-1,2,4-oxadiazoles were synthesized from the reaction of amidoximes and chloroacetyl chloride. These compounds were then converted into 5-aminomethyl-3-aryl-1,2,4-oxadiazoles by Gabriel amine synthesis in two steps. The reaction of amine compounds with phenyl isocyanate and phenyl isothiocyanate in THF at room temperature were performed to afford urea and thiourea compounds respectively, in good yields. The structures of the synthesized compounds were elucidated by FTIR, 1H NMR, 13C NMR and elemental analysis techniques. At the final step of the work, twenty new urea and thiourea compounds were tested for their in vitro antimicrobial activities, against two gram-positive (Staphylococcus aureus ATCC 25923, Staphylococcus aureus ATCC 33591) and two gram-negative (Escherichia coli ATCC 25922, Escherichia coli ATCC 0157: H7) bacterial strains by minimum inhibitory concentration (MIC) method. Ciprofloxacin and Chloramphenicol were used as reference antibiotics. It was observed that the compounds do not possess significant antimicrobial activities against the tested bacterias.