Activity of N-Phenylpiperazine Derivatives Against Bacterial
and Fungal Pathogens

J 2019

Activity of N-Phenylpiperazine Derivatives Against Bacterial and Fungal Pathogens

POSPÍŠILOVÁ, Šárka, Pavlína MARVANOVÁ, Jakub TREML, Agnes M. MORICZ, Peter G. OTT et. al.

Základní údaje

Originální název

Activity of N-Phenylpiperazine Derivatives Against Bacterial and Fungal Pathogens

Autoři

POSPÍŠILOVÁ, Šárka (203 Česká republika), Pavlína MARVANOVÁ (203 Česká republika), Jakub TREML (203 Česká republika), Agnes M. MORICZ (348 Maďarsko), Peter G. OTT (348 Maďarsko), Petr MOKRÝ (203 Česká republika), Klára ODEHNALOVÁ (203 Česká republika), Ondrej ŠEDO (203 Česká republika, garant, domácí), Alois ČÍŽEK (203 Česká republika) a Josef JAMPÍLEK (203 Česká republika)

Vydání

CURRENT PROTEIN & PEPTIDE SCIENCE, Bentham Science Publishers, 2019, 1389-2037

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.520

Kód RIV

RIV/00216224:14740/19:00107988

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.2174/1389203720666190913114041

UT WoS

000492730400011

Klíčová slova anglicky

N-phenylpiperazines; synthesis; lipophilicity; dissociation constant; antimycobacterials; antifungals; cytotoxicity

Štítky

CF PROT, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 9. 10. 2024 14:10, Ing. Martina Blahová

Anotace

V originále

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.

Návaznosti

GBP206/12/G151, projekt VaV

Název: Centrum nových přístupů k bioanalýze a molekulární diagnostice

LM2015043, projekt VaV

Název: Česká infrastruktura pro integrativní strukturní biologii (Akronym: CIISB)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Czech Infrastructure for Integrative Structural Biology

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

90043, velká výzkumná infrastruktura

Název: CIISB

Citovat

POSPÍŠILOVÁ, Šárka, Pavlína MARVANOVÁ, Jakub TREML, Agnes M. MORICZ, Peter G. OTT, Petr MOKRÝ, Klára ODEHNALOVÁ, Ondrej ŠEDO, Alois ČÍŽEK a Josef JAMPÍLEK. Activity of N-Phenylpiperazine Derivatives Against Bacterial and Fungal Pathogens. CURRENT PROTEIN & PEPTIDE SCIENCE. Bentham Science Publishers, 2019, roč. 20, č. 11, s. 1119-1129. ISSN 1389-2037. Dostupné z: https://dx.doi.org/10.2174/1389203720666190913114041.

@article{1601825,
   author = {Pospíšilová, Šárka and Marvanová, Pavlína and Treml, Jakub and Moricz, Agnes M. and Ott, Peter G. and Mokrý, Petr and Odehnalová, Klára and Šedo, Ondrej and Čížek, Alois and Jampílek, Josef},
   article_number = {11},
   doi = {http://dx.doi.org/10.2174/1389203720666190913114041},
   keywords = {N-phenylpiperazines; synthesis; lipophilicity; dissociation constant; antimycobacterials; antifungals; cytotoxicity},
   language = {eng},
   issn = {1389-2037},
   journal = {CURRENT PROTEIN & PEPTIDE SCIENCE},
   title = {Activity of N-Phenylpiperazine Derivatives Against Bacterial and Fungal Pathogens},
   url = {http://dx.doi.org/10.2174/1389203720666190913114041},
   volume = {20},
   year = {2019}
}

TY  - JOUR
ID  - 1601825
AU  - Pospíšilová, Šárka - Marvanová, Pavlína - Treml, Jakub - Moricz, Agnes M. - Ott, Peter G. - Mokrý, Petr - Odehnalová, Klára - Šedo, Ondrej - Čížek, Alois - Jampílek, Josef
PY  - 2019
TI  - Activity of N-Phenylpiperazine Derivatives Against Bacterial and Fungal Pathogens
JF  - CURRENT PROTEIN & PEPTIDE SCIENCE
VL  - 20
IS  - 11
SP  - 1119-1129
EP  - 1119-1129
PB  - Bentham Science Publishers
SN  - 13892037
KW  - N-phenylpiperazines
KW  - synthesis
KW  - lipophilicity
KW  - dissociation constant
KW  - antimycobacterials
KW  - antifungals
KW  - cytotoxicity
UR  - http://dx.doi.org/10.2174/1389203720666190913114041
L2  - http://dx.doi.org/10.2174/1389203720666190913114041
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 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.
ER  -

POSPÍŠILOVÁ, Šárka, Pavlína MARVANOVÁ, Jakub TREML, Agnes M. MORICZ, Peter G. OTT, Petr MOKRÝ, Klára ODEHNALOVÁ, Ondrej ŠEDO, Alois ČÍŽEK a Josef JAMPÍLEK. Activity of N-Phenylpiperazine Derivatives Against Bacterial and Fungal Pathogens. \textit{CURRENT PROTEIN \&{} PEPTIDE SCIENCE}. Bentham Science Publishers, 2019, roč.~20, č.~11, s.~1119-1129. ISSN~1389-2037. Dostupné z: https://dx.doi.org/10.2174/1389203720666190913114041.

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