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
Sergii Demchenko,
Roman Lesyk,
Oleh Yadlovskyi,
Johannes Zuegg,
Alysha G. Elliott,
Iryna Drapak,
Yuliia Fedchenkova,
Zinaida Suvorova,
Anatolii Demchenko
Affiliations
Sergii Demchenko
Institute of Pharmacology and Toxicology, Antona Tsedika 14, 03057 Kyiv, Ukraine
Roman Lesyk
Department of Public Health, Dietetics and Lifestyle Disorders, Faculty of Medicine, University of Information Technology and Management in Rzeszow, 35-225 Rzeszow, Poland
Oleh Yadlovskyi
Institute of Pharmacology and Toxicology, Antona Tsedika 14, 03057 Kyiv, Ukraine
Johannes Zuegg
The Community for Open Antimicrobial Drug Discovery (CO-ADD), Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane 4072, Australia
Alysha G. Elliott
The Community for Open Antimicrobial Drug Discovery (CO-ADD), Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane 4072, Australia
Iryna Drapak
Department of General, Inorganic, Physical and Colloidal Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, Ukraine
Yuliia Fedchenkova
Department of Chemistry and Pharmacy, Nizhyn Mykola Gogol State University, 16600 Nizhyn, Ukraine
Zinaida Suvorova
Institute of Pharmacology and Toxicology, Antona Tsedika 14, 03057 Kyiv, Ukraine
Anatolii Demchenko
Institute of Pharmacology and Toxicology, Antona Tsedika 14, 03057 Kyiv, Ukraine
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).
