Activity of N-Phenylpiperazine Derivatives Against Bacterial and Fungal Pathogens

This publication doesn't include Faculty of Arts. It includes Central European Institute of Technology. Official publication website can be found on muni.cz.

Authors

POSPÍŠILOVÁ Šárka MARVANOVÁ Pavlína TREML Jakub MORICZ Agnes M. OTT Peter G. MOKRÝ Petr ODEHNALOVÁ Klára ŠEDO Ondrej ČÍŽEK Alois JAMPÍLEK Josef

Year of publication 2019
Type Article in Periodical
Magazine / Source CURRENT PROTEIN & PEPTIDE SCIENCE
MU Faculty or unit

Central European Institute of Technology

Citation
Web http://dx.doi.org/10.2174/1389203720666190913114041
Doi http://dx.doi.org/10.2174/1389203720666190913114041
Keywords N-phenylpiperazines; synthesis; lipophilicity; dissociation constant; antimycobacterials; antifungals; cytotoxicity
Description Background: As the bacterial resistance to antibacterial chemotherapeutics is one of the greatest problems in modern medicine, efforts are made to develop new antimicrobial drugs. Compounds with a piperazine ring have proved to be promising agents against various pathogens. Objective: The aim of the study was to prepare a series of new N-phenylpiperazines and determine their activity against various pathogens. Method: Target compounds were prepared by multi-step synthesis starting from an appropriate substituted acid to an oxirane intermediate reacting with 1-(4-nitrophenyl)piperazine. Lipophilicity and pK(a) values were experimentally determined. Other molecular parameters were calculated. The inhibitory activity of the target compounds against Staphylococcus aureus, four mycobacteria strains, Bipolaris sorokiniana, and Fusarium avenaceum was tested. In vitro antiproliferative activity was determined on a THP-1 cell line, and toxicity against plant was determined using Nicotiana tabacum. Results: In general, most compounds demonstrated only moderate effects. 1-(2-Hydroxy-3-{[4-(propan-2-yloxy)benzoyl]oxy}propyl)-4-(4-nitropbenyl)piperazinediium dichloride and 1-{3-[(4-butoxybenzoyl)-oxy]-2-hydroxypropyl} -4-(4-nitrophenyl)piperazinediium dichloride showed the highest inhibition activity against M. kansasii (MIC - 15.4 and 15.0 mu M, respectively) and the latter also against M. marinum (MIC = 15.0 mu M). 1-(2-Hydroxy-3-{[4-(2-propoxyethoxy)benzoyl]oxy}propyl)-4-(4-nitrophenyl)piperazinediium dichloride had the highest activity against F. avenaceum (MIC - 14.2 mu M). All the compounds showed only insignificant toxic effects on human and plant cells. Conclusion: Ten new 1-(4-nitrophenyl)piperazine derivatives were prepared and analyzed, and their antistaphylococcal, antimycobacterial, and antifungal activities were determined. The activity against M. kansasii was positively influenced by higher lipophilicity, the electron-donor properties of substituent R and a lower dissociation constant. The exact mechanism of action will be investigated in follow-up studies.
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