Dibasic Derivatives of Phenylcarbamic Acid as Prospective
Antibacterial Agents Interacting with Cytoplasmic Membrane

J 2020

Dibasic Derivatives of Phenylcarbamic Acid as Prospective Antibacterial Agents Interacting with Cytoplasmic Membrane

POSPISILOVA, S., Ivan MALÍK, K. BEZOUSKOVA, Tereza KAUEROVÁ, Peter KOLLÁR et. al.

Basic information

Original name

Dibasic Derivatives of Phenylcarbamic Acid as Prospective Antibacterial Agents Interacting with Cytoplasmic Membrane

Authors

POSPISILOVA, S., Ivan MALÍK (703 Slovakia), K. BEZOUSKOVA, Tereza KAUEROVÁ (203 Czech Republic, belonging to the institution), Peter KOLLÁR (203 Czech Republic, belonging to the institution), Jozef CSÖLLEI (203 Czech Republic, belonging to the institution), M. ORAVEC, Alois ČÍŽEK (203 Czech Republic) and J. JAMPILEK

Edition

Antibiotics-Basel, BASEL, MDPI, 2020, 2079-6382

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.639

RIV identification code

RIV/00216224:14160/20:00116288

Organization unit

Faculty of Pharmacy

DOI

http://dx.doi.org/10.3390/antibiotics9020064

UT WoS

000519242200040

Keywords in English

carbamate; antibacterial; synergy; antibiofilm activity; structure-activity relationships

Abstract

V originále

1-[2-[({[2-/3-(Alkoxy)phenyl]amino}carbonyl)oxy]-3-(dipropylammonio)propyl]pyrrolidinium/azepan- ium oxalates or dichlorides (alkoxy = butoxy to heptyloxy) were recently described as very promising antimycobacterial agents. These compounds were tested in vitro against Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 (reference and control strains), three methicillin-resistant isolates of S. aureus, and three isolates of vancomycin-resistant E. faecalis. 1-[3-(Dipropylammonio)-2-({[3-(pentyloxy-/hexyloxy-/heptyloxy)phenyl]carbamoyl}oxy)propyl]pyrrolidinium dichlorides showed high activity against staphylococci and enterococci comparable with or higher than that of used controls (clinically used antibiotics and antiseptics). The screening of the cytotoxicity of the compounds as well as the used controls was performed using human monocytic leukemia cells. IC50 values of the most effective compounds ranged from ca. 3.5 to 6.3 mu M, thus, it can be stated that the antimicrobial effect is closely connected with their cytotoxicity. The antibacterial activity is based on the surface activity of the compounds that are influenced by the length of their alkoxy side chain, the size of the azacyclic system, and hydro-lipophilic properties, as proven by in vitro experiments and chemometric principal component analyses. Synergistic studies showed the increased activity of oxacillin, gentamicin, and vancomycin, which could be explained by the direct activity of the compounds against the bacterial cell wall. All these compounds demonstrate excellent antibiofilm activity, when they inhibit and disrupt the biofilm of S. aureus in concentrations close to minimum inhibitory concentrations against planktonic cells. Expected interactions of the compounds with the cytoplasmic membrane are proven by in vitro crystal violet uptake assays.

Citovat

POSPISILOVA, S., Ivan MALÍK, K. BEZOUSKOVA, Tereza KAUEROVÁ, Peter KOLLÁR, Jozef CSÖLLEI, M. ORAVEC, Alois ČÍŽEK and J. JAMPILEK. Dibasic Derivatives of Phenylcarbamic Acid as Prospective Antibacterial Agents Interacting with Cytoplasmic Membrane. Antibiotics-Basel. BASEL: MDPI, 2020, vol. 9, No 2, p. 1-22. ISSN 2079-6382. Available from: https://dx.doi.org/10.3390/antibiotics9020064.

@article{1675887,
   author = {Pospisilova, S. and Malík, Ivan and Bezouskova, K. and Kauerová, Tereza and Kollár, Peter and Csöllei, Jozef and Oravec, M. and Čížek, Alois and Jampilek, J.},
   article_location = {BASEL},
   article_number = {2},
   doi = {http://dx.doi.org/10.3390/antibiotics9020064},
   keywords = {carbamate; antibacterial; synergy; antibiofilm activity; structure-activity relationships},
   language = {eng},
   issn = {2079-6382},
   journal = {Antibiotics-Basel},
   title = {Dibasic Derivatives of Phenylcarbamic Acid as Prospective Antibacterial Agents Interacting with Cytoplasmic Membrane},
   url = {https://www.mdpi.com/2079-6382/9/2/64/htm},
   volume = {9},
   year = {2020}
}

TY  - JOUR
ID  - 1675887
AU  - Pospisilova, S. - Malík, Ivan - Bezouskova, K. - Kauerová, Tereza - Kollár, Peter - Csöllei, Jozef - Oravec, M. - Čížek, Alois - Jampilek, J.
PY  - 2020
TI  - Dibasic Derivatives of Phenylcarbamic Acid as Prospective Antibacterial Agents Interacting with Cytoplasmic Membrane
JF  - Antibiotics-Basel
VL  - 9
IS  - 2
SP  - 1-22
EP  - 1-22
PB  - MDPI
SN  - 20796382
KW  - carbamate
KW  - antibacterial
KW  - synergy
KW  - antibiofilm activity
KW  - structure-activity relationships
UR  - https://www.mdpi.com/2079-6382/9/2/64/htm
L2  - https://www.mdpi.com/2079-6382/9/2/64/htm
N2  - 1-[2-[({[2-/3-(Alkoxy)phenyl]amino}carbonyl)oxy]-3-(dipropylammonio)propyl]pyrrolidinium/azepan- ium oxalates or dichlorides (alkoxy = butoxy to heptyloxy) were recently described as very promising antimycobacterial agents. These compounds were tested in vitro against Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 (reference and control strains), three methicillin-resistant isolates of S. aureus, and three isolates of vancomycin-resistant E. faecalis. 1-[3-(Dipropylammonio)-2-({[3-(pentyloxy-/hexyloxy-/heptyloxy)phenyl]carbamoyl}oxy)propyl]pyrrolidinium dichlorides showed high activity against staphylococci and enterococci comparable with or higher than that of used controls (clinically used antibiotics and antiseptics). The screening of the cytotoxicity of the compounds as well as the used controls was performed using human monocytic leukemia cells. IC50 values of the most effective compounds ranged from ca. 3.5 to 6.3 mu M, thus, it can be stated that the antimicrobial effect is closely connected with their cytotoxicity. The antibacterial activity is based on the surface activity of the compounds that are influenced by the length of their alkoxy side chain, the size of the azacyclic system, and hydro-lipophilic properties, as proven by in vitro experiments and chemometric principal component analyses. Synergistic studies showed the increased activity of oxacillin, gentamicin, and vancomycin, which could be explained by the direct activity of the compounds against the bacterial cell wall. All these compounds demonstrate excellent antibiofilm activity, when they inhibit and disrupt the biofilm of S. aureus in concentrations close to minimum inhibitory concentrations against planktonic cells. Expected interactions of the compounds with the cytoplasmic membrane are proven by in vitro crystal violet uptake assays.
ER  -

POSPISILOVA, S., Ivan MALÍK, K. BEZOUSKOVA, Tereza KAUEROVÁ, Peter KOLLÁR, Jozef CSÖLLEI, M. ORAVEC, Alois ČÍŽEK and J. JAMPILEK. Dibasic Derivatives of Phenylcarbamic Acid as Prospective Antibacterial Agents Interacting with Cytoplasmic Membrane. \textit{Antibiotics-Basel}. BASEL: MDPI, 2020, vol.~9, No~2, p.~1-22. ISSN~2079-6382. Available from: https://dx.doi.org/10.3390/antibiotics9020064.

Detailed Information on Publication Record