New Pyrazolo-Benzimidazole Mannich Bases with Antimicrobial and Antibiofilm Activities
Christina Zalaru,
Florea Dumitrascu,
Constantin Draghici,
Isabela Tarcomnicu,
Maria Marinescu,
George Mihai Nitulescu,
Rodica Tatia,
Lucia Moldovan,
Marcela Popa,
Mariana Carmen Chifiriuc
Affiliations
Christina Zalaru
Department of Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, 90-92 Panduri Road, 030018 Bucharest, Romania
Florea Dumitrascu
“C.D. Nenitescu” Institute of Organic and Supramolecular Chemistry Romanian Academy, 202 B Spl. Independentei, 060023 Bucharest, Romania
Constantin Draghici
“C.D. Nenitescu” Institute of Organic and Supramolecular Chemistry Romanian Academy, 202 B Spl. Independentei, 060023 Bucharest, Romania
Isabela Tarcomnicu
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, No. 1 Dr. Calistrat Grozovici Street, 021105 Bucharest, Romania
Maria Marinescu
Department of Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, 90-92 Panduri Road, 030018 Bucharest, Romania
George Mihai Nitulescu
Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania
Rodica Tatia
Department of Cellular and Molecular Biology, National Institute of Research and Development for Biological Sciences, 296 Splaiul Independenţei, 060031 Bucharest, Romania
Lucia Moldovan
Department of Cellular and Molecular Biology, National Institute of Research and Development for Biological Sciences, 296 Splaiul Independenţei, 060031 Bucharest, Romania
Marcela Popa
Department of Microbiology, Faculty of Biology, University of Bucharest, 1-3 Aleea Portocalelor St., 60101 Bucharest, Romania
Mariana Carmen Chifiriuc
Department of Microbiology, Faculty of Biology, University of Bucharest, 1-3 Aleea Portocalelor St., 60101 Bucharest, Romania
A new series of pyrazolo-benzimidazole hybrid Mannich bases were synthesized, characterized by 1H-NMR, 13C-NMR, IR, UV-Vis, MS, and elemental analysis. In vitro cytotoxicity of the new compounds studied on fibroblast cells showed that the newly synthesized pyrazolo-benzimidazole hybrid derivatives were noncytotoxic until the concentration of 1 μM and two compounds presented a high degree of biocompatibility. The antibacterial and antibiofilm activity of the newly synthesized compounds was assayed on Gram-positive Staphylococcus aureus ATCC25923, Enterococcus faecalis ATCC29212, and Gram-negative Pseudomonas aeruginosa ATCC27853, Escherichia coli ATCC25922 strains. All synthesized compounds 5a–g are more active against all three tested bacterial strains Staphylococcus aureus ATCC25923, Enterococcus faecalis ATCC29212, and Escherichia coli ATCC25922 than reference drugs (Metronidazole, Nitrofurantoin), with the exception of compounds 5d and 5g, which are less active compared to Nitrofurantoin, and all synthesized compounds 5a–g are more active against Pseudomonas aeruginosa ATCC27853 compared to reference drugs (Metronidazole, Nitrofurantoin). Compound 5f showed the best activity against Staphylococcus aureus ATCC 25923, with a MIC of 150 μg/mL and has also inhibited the biofilm formed by all the bacterial strains, having an MBIC of 310 µg/mL compared to the reference drugs (Metronidazole, Nitrofurantoin).
