The Structure–Antimicrobial Activity Relationships of a Promising Class of the Compounds Containing the N-Arylpiperazine Scaffold
Ivan Malík,
Jozef Csöllei,
Josef Jampílek,
Lukáš Stanzel,
Iveta Zadražilová,
Jan Hošek,
Šárka Pospíšilová,
Alois Čížek,
Aidan Coffey,
Jim O’Mahony
Affiliations
Ivan Malík
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, Bratislava SK-832 32, Slovak Republic
Jozef Csöllei
Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences in Brno, Palackého 1946/1, Brno CZ-612 42, Czech Republic
Josef Jampílek
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, Bratislava SK-832 32, Slovak Republic
Lukáš Stanzel
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, Bratislava SK-832 32, Slovak Republic
Iveta Zadražilová
Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences in Brno, Palackého 1946/1, Brno CZ-612 42, Czech Republic
Jan Hošek
Department of Molecular Biology and Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences in Brno, Palackého 1946/1, Brno CZ-612 42, Czech Republic
Šárka Pospíšilová
Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences in Brno, Palackého 1946/1, Brno CZ-612 42, Czech Republic
Alois Čížek
Department of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences in Brno, Palackého 1946/1, Brno CZ-612 42, Czech Republic
Aidan Coffey
Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork T12 P928, Ireland
Jim O’Mahony
Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork T12 P928, Ireland
This research was focused on in silico characterization and in vitro biological testing of the series of the compounds carrying a N-arylpiperazine moiety. The in silico investigation was based on the prediction of electronic, steric and lipohydrophilic features. The molecules were screened against Mycobacterium avium subsp. paratuberculosis CIT03, M. smegmatis ATCC 700084, M. kansasii DSM 44162, M. marinum CAMP 5644, Staphylococcus aureus ATCC 29213, methicillin-resistant S. aureus 63718, Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29212, Candida albicans CCM 8261, C. parapsilosis CCM 8260 and C. krusei CCM 8271, respectively, by standardized microdilution methods. The eventual antiproliferative (cytotoxic) impact of those compounds was examined on a human monocytic leukemia THP-1 cell line, as a part of the biological study. Promising potential against M. kansasii was found for 1-[3-(3-ethoxyphenylcarbamoyl)oxy-2-hydroxypropyl]-4-(3-trifluoromethylphenyl)piperazin-1-ium chloride (MIC = 31.75 μM), which was comparable to the activity of isoniazid (INH; MIC = 29.17 μM). Moreover, 1-{2-hydroxy-3-(3-methoxyphenylcarbamoyl)oxy)propyl}-4-(4-fluorophenyl)piperazin-1-ium chloride was even more effective (MIC = 17.62 μM) against given mycobacterium. Among the tested N-arylpiperazines, 1-{2-hydroxy-3-(4-methoxyphenylcarbamoyl)oxy)propyl}-4-(3-trifluorometh-ylphenyl)piperazin-1-ium chloride was the most efficient against M. marinum (MIC = 65.32 μM). One of the common features of all investigated substances was their insignificant antiproliferative (i.e., non-cytotoxic) effect. The study discussed structure–antimicrobial activity relationships considering electronic, steric and lipophilic properties.