Synthesis, Antibacterial and Antifungal Activity of New 3-Aryl-5<i>H</i>-pyrrolo[1,2-<i>a</i>]imidazole and 5<i>H</i>-Imidazo[1,2-<i>a</i>]azepine Quaternary Salts

Abstract

A series of novel 3-aryl-5H-pyrrolo[1,2-a]imidazole and 5H-imidazo[1,2-a]azepine quaternary salts were synthesized in 58–85% yields via the reaction of 3-aryl-6, 7-dihydro-5H-pyrrolo[1,2-a]imidazoles or 3-aryl-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepines and various alkylating reagents. All compounds were characterized by 1H NMR, 13C NMR, and LC-MS. The conducted screening studies of the in vitro antimicrobial activity of the new quaternary salts derivatives established that 15 of the 18 newly synthesized compounds show antibacterial and antifungal activity. Synthesized 3-(3,4-dichlorohenyl)-1-[(4-phenoxyphenylcarbamoyl)-methyl]-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-1-ium chloride 6c possessed a broad activity spectrum towards Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Cryptococcus neoformans, with a high hemolytic activity against human red blood cells and cytotoxicity against HEK-293. However, compound 6c is characterized by a low in vivo toxicity in mice (LD50 > 2000 mg/kg).

Keywords

• 5<i>H</i>-pyrrolo[1,2-<i>a</i>]imidazoles
• 5<i>H</i>-imidazo[1,2-<i>a</i>]azepines
• quaternary salts
• antibacterial activity
• antifungal activity
• in vitro tests