No abstract

A new series of metronidazole derivatives containing piperazine rings were prepared via the reaction of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)acetyl chloride with selected substituted piperazines in the presence of a base. Structures of the new compounds were confirmed by NMR and MS spectral data and by elemental analyses. The antibacterial and anti-parasitic activities of these compounds were evaluated in vitro. Some of the newly synthesized compounds exhibited superior activity against Clostridium sporogenes bacteria compared to the standard drug metronidazole. On the other hand, other derivatives exhibited remarkable antigiardial activity and were found to be more active than metronidazole with IC 50 ranging from 1.8 to 6.7 lg/dm 3 . 1-Ethyl-4-[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]piperazine also exhibited antigiardial activity with similar IC 50 value (7.6 lg/cm 3 ) as compared to the reference drug metronidazole (IC 50 = 7.4 lg/cm 3 ). Similarly, several of the new compounds exhibited significant antitrichomonal activity and found to be more active than metronidazole with IC 50 ranging from 6.7 to 8.65 lg/cm 3 as compared to the reference drug metronidazole (8.9 lg/cm 3 ).

A number of novel bicinnolines containing piperazine moieties, 4a–o, were synthesized via polyphosphoric acid‐catalyzed intramolecular cyclization of the respective acyl amidrazone derivatives (3a–o). On the other hand, the amidrazones (3a–o) were prepared by reaction of N′,N″‐(biphenyl‐4,4′‐diyl)bis(2‐oxopropane hydrazonoyl chloride) (2) with the appropriate cyclic sec‐amines in the presence of trimethylamine in absolute ethanol. Structures of the newly synthesized compounds were confirmed by NMR and mass spectral data. The antitumor activity of compounds 4a–o was evaluated in vitro on human breast cancer MDA‐231 by a cell viability assay. Results revealed that compounds 4k, 4n, and 4o exhibit potential cytotoxic effects (>70%) on the cancer cells. Additionally, the antimicrobial activity of compounds 4a–o was evaluated against three clinical microbial strains: Escherichia coli (Gram‐negative bacteria), Staphylococcus aureus (Gram‐positive bacteria), and Candida albicans (fungi/yeast). Results revealed that compounds 4e and 4k exhibit good activity against all three strains included in the study and that compound 4d displays excellent activity against S. aureus strain with a minimum inhibitory concentration value of 0.187 mg/mL.