The Structure-Antimicrobial Activity Relationships of a Promising Class of the Compounds Containing the N-Arylpiperazine Scaffold.
This research was focused onin silicocharacterization andin vitrobiological testing of the series of the compounds carrying aN-arylpiperazine moiety. Thein silicoinvestigation was based on the prediction of electronic, steric and lipohydrophilic features. The molecules were screened againstMycobacterium aviumsubsp.paratuberculosisCIT03,M. smegmatisATCC 700084,M. kansasiiDSM 44162,M. marinumCAMP 5644,Staphylococcus aureusATCC 29213, methicillin-resistantS. aureus63718,Escherichia coliATCC 25922,Enterococcus faecalisATCC 29212,Candida albicansCCM 8261,C. parapsilosisCCM 8260 andC. kruseiCCM 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 againstM. kansasiiwas 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 givenmycobacterium. Among the testedN-arylpiperazines, 1-{2-hydroxy-3-(4-methoxyphenylcarbamoyl)oxy)propyl}-4-(3-trifluorometh-ylphenyl)piperazin-1-ium chloride was the most efficient againstM. 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.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, Bratislava SK-832 32, Slovak Republic. malikivan001@gmail.com.
Ivan
I
Malík
Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences in Brno, Palackého 1946/1, Brno CZ-612 42, Czech Republic. csolleij@cfu.cz.
Jozef
J
Csöllei
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, Bratislava SK-832 32, Slovak Republic. josef.jampilek@gmail.com.
Josef
J
Jampílek
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, Bratislava SK-832 32, Slovak Republic. lukasstanzel@gmail.com.
Lukáš
L
Stanzel
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. zadrazilova.iveta@seznam.cz.
Iveta
I
Zadražilová
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. hhosek@gmail.com.
Jan
J
Hošek
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. sharka.pospisilova@gmail.com.
Šárka
Š
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. cizeka@vfu.cz.
Alois
A
Čížek
Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork T12 P928, Ireland. aidan.coffey@cit.ie.
Aidan
A
Coffey
Department of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork T12 P928, Ireland. jim.omahony@cit.ie.
Jim
J
O'Mahony
Mycobacterium kansasii; Mycobacterium marinum; N-arylpiperazines; electronic properties; lipophilicity; structure–activity
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