Synthesis and Antimicrobial Evaluation of Deuterated Analogues of Metronidazole

Abstract

Metronidazole is a commonly used antibiotic for anaerobic bacterial infections, protozoal infections, and microaerophilic bacterial infections by interacting with DNA and thereby inhibiting the protein synthesis. Metronidazole is administered orally, intravenously, or topically and has a half-life of 6.5 ± 2.9 hours. A number of studies have recently been conducted on the selective substitution of hydrogen with deuterium, which increases the bond strength thereby increasing the biological half-life and, consequently, the drug's metabolic stability. In an attempt to check whether the deuterated metronidazole possessed similar pharmacological activity as that of metronidazole, deuterated metronidazole was synthesised using deuterium oxide in the presence of benzoic acid under nitrogen atmosphere. The synthesised deuterated metronidazole was characterised by IR, 1HNMR and mass spectroscopy and were tested for antibacterial, antifungal, and anti-tubercular activities. The metronidazole and its deuterated compound showed equipotent antifungal activity and aerobic antibacterial activity. Also, when compared with the non-deuterated compound, deuterated metronidazole exhibited better anaerobic antibacterial and anti-tubercular activity.