Synthesis and Pharmacological Characterization of Metronidazole-Oxadiazole Derivatives

BACKGROUND: The use of antibiotics with or without prescription is increasing worldwide. With certain limitations, metronidazole (MTZ) is extensively used as an antibacterial and antiparasitic drug. Derivatives of 1,2,4-oxadiazole (ODZ) are used to modify the chemical structure of drugs. The present study aimed to synthesize new MTZ-ODZ derivatives that could potentially lead to new medications. METHODS: The reaction of MTZ with ethyl chloroacetate and potassium carbonate anhydrous was used to produce compound 7. This compound was treated with hydrazine hydrate in methanol to obtain compound 8. Carbon disulfide and potassium hydroxide were then added to obtain compound 9, which was then mixed with various α-haloketones to obtain compounds 10a to 10f. Subsequently, the structures of the new MTZ-ODZ derivatives were determined. RESULTS: All new compounds exhibited excellent activity against all tested organisms. The synthesized compounds showed a significant radical scavenging activity. The IC(50) value for compounds 10a, 10b, 10c, 10d, 10e, and 10f was 70.42±0.15, 70.52±0.54, 85.21±0.85, 80.10±0.46, 82.52±0.13, and 70.45±0.12 g/mL, respectively. In terms of antigiardial activity, the IC(50) value for compounds 10a,10b, 10c, and 10d ranged from 1.31±0.11 µM to 2.26±0.49 µM. In contrast, the IC(50) for MTZ was 3.71±0.27 µM. Compound 10f showed the highest antigiardial activity with an IC(50) value of 0.88±0.52 µM. CONCLUSION: Most of the MTZ-ODZ derivatives showed high radical scavenging activity in the benzene ring due to the activation of certain groups, such as OCH(3), NO(2), and OH. The results suggest that the newly synthesized compounds could be used as an antiparasitic drug.