Azine derivatives against bacterial and fungal

Sarka Pospisilova, Pavlina Marvanova, Jakub Treml, Agnes M. Moricz, Peter G. Ott, Petr Mokry, Klara Odehnalova, Ondrej Sedo, Alois Cizek, Josef Jampilek

Research output: Article

1 Citation (Scopus)

Abstract

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 pKa 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-nitrophenyl)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 µM, respectively) and the latter also against M. marinum (MIC = 15.0 µM). 1-(2-Hydroxy-3-{[4-(2-propoxyethoxy)benzoyl]oxy}propyl)-4-(4-nitrophenyl)pipera-zinediium dichloride had the highest activity against F. avenaceum (MIC = 14.2 µM). 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.

Original languageEnglish
Pages (from-to)1119-1129
Number of pages11
JournalCurrent Protein and Peptide Science
Volume20
Issue number11
DOIs
Publication statusPublished - jan. 1 2019

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Pathogens
Derivatives
Ethylene Oxide
Modern 1601-history
Poisons
Fusarium
Plant Cells
Mycobacterium
Medicine
Tobacco
Toxicity
Staphylococcus aureus
Cells
Electrons
Cell Line
Acids
Pharmaceutical Preparations
4-nitrophenyl
1-(4-nitrophenyl)piperazine
phenylpiperazine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Azine derivatives against bacterial and fungal. / Pospisilova, Sarka; Marvanova, Pavlina; Treml, Jakub; Moricz, Agnes M.; Ott, Peter G.; Mokry, Petr; Odehnalova, Klara; Sedo, Ondrej; Cizek, Alois; Jampilek, Josef.

In: Current Protein and Peptide Science, Vol. 20, No. 11, 01.01.2019, p. 1119-1129.

Research output: Article

Pospisilova, S, Marvanova, P, Treml, J, Moricz, AM, Ott, PG, Mokry, P, Odehnalova, K, Sedo, O, Cizek, A & Jampilek, J 2019, 'Azine derivatives against bacterial and fungal', Current Protein and Peptide Science, vol. 20, no. 11, pp. 1119-1129. https://doi.org/10.2174/1389203720666190913114041
Pospisilova, Sarka ; Marvanova, Pavlina ; Treml, Jakub ; Moricz, Agnes M. ; Ott, Peter G. ; Mokry, Petr ; Odehnalova, Klara ; Sedo, Ondrej ; Cizek, Alois ; Jampilek, Josef. / Azine derivatives against bacterial and fungal. In: Current Protein and Peptide Science. 2019 ; Vol. 20, No. 11. pp. 1119-1129.
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abstract = "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 pKa 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-nitrophenyl)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 µM, respectively) and the latter also against M. marinum (MIC = 15.0 µM). 1-(2-Hydroxy-3-{[4-(2-propoxyethoxy)benzoyl]oxy}propyl)-4-(4-nitrophenyl)pipera-zinediium dichloride had the highest activity against F. avenaceum (MIC = 14.2 µM). 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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author = "Sarka Pospisilova and Pavlina Marvanova and Jakub Treml and Moricz, {Agnes M.} and Ott, {Peter G.} and Petr Mokry and Klara Odehnalova and Ondrej Sedo and Alois Cizek and Josef Jampilek",
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T1 - Azine derivatives against bacterial and fungal

AU - Pospisilova, Sarka

AU - Marvanova, Pavlina

AU - Treml, Jakub

AU - Moricz, Agnes M.

AU - Ott, Peter G.

AU - Mokry, Petr

AU - Odehnalova, Klara

AU - Sedo, Ondrej

AU - Cizek, Alois

AU - Jampilek, Josef

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 pKa 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-nitrophenyl)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 µM, respectively) and the latter also against M. marinum (MIC = 15.0 µM). 1-(2-Hydroxy-3-{[4-(2-propoxyethoxy)benzoyl]oxy}propyl)-4-(4-nitrophenyl)pipera-zinediium dichloride had the highest activity against F. avenaceum (MIC = 14.2 µM). 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.

AB - 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 pKa 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-nitrophenyl)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 µM, respectively) and the latter also against M. marinum (MIC = 15.0 µM). 1-(2-Hydroxy-3-{[4-(2-propoxyethoxy)benzoyl]oxy}propyl)-4-(4-nitrophenyl)pipera-zinediium dichloride had the highest activity against F. avenaceum (MIC = 14.2 µM). 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.

KW - Antifungals

KW - Antimycobacterials

KW - Cytotoxicity

KW - Dissociation constant

KW - Lipophilicity

KW - N-phenylpiperazines

KW - Synthesis

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