Dibasic Derivatives of Phenylcarbamic Acid as Prospective Antibacterial Agents Interacting with Cytoplasmic Membrane
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 <i>Staphylococcus aureus&...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-02-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/9/2/64 |
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| author | Šárka Pospíšilová Ivan Malík Kristyna Bezouskova Tereza Kauerova Peter Kollar Jozef Csöllei Michal Oravec Alois Cizek Josef Jampilek |
| author_facet | Šárka Pospíšilová Ivan Malík Kristyna Bezouskova Tereza Kauerova Peter Kollar Jozef Csöllei Michal Oravec Alois Cizek Josef Jampilek |
| author_sort | Šárka Pospíšilová |
| collection | DOAJ |
| description | 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 <i>Staphylococcus aureus</i> ATCC 29213, <i>Enterococcus faecalis</i> ATCC 29212 (reference and control strains), three methicillin-resistant isolates of <i>S. aureus</i>, and three isolates of vancomycin-resistant <i>E. faecalis</i>. 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. IC<sub>50</sub> values of the most effective compounds ranged from ca. 3.5 to 6.3 µM, 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 <i>S. aureus</i> 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. |
| first_indexed | 2024-04-14T00:14:00Z |
| format | Article |
| id | doaj.art-26cbd3b661914abfbd60c49d2b562ecc |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-04-14T00:14:00Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-26cbd3b661914abfbd60c49d2b562ecc2022-12-22T02:23:12ZengMDPI AGAntibiotics2079-63822020-02-01926410.3390/antibiotics9020064antibiotics9020064Dibasic Derivatives of Phenylcarbamic Acid as Prospective Antibacterial Agents Interacting with Cytoplasmic MembraneŠárka Pospíšilová0Ivan Malík1Kristyna Bezouskova2Tereza Kauerova3Peter Kollar4Jozef Csöllei5Michal Oravec6Alois Cizek7Josef Jampilek8Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacky University, Slechtitelu 27, 783 71 Olomouc, Czech RepublicDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University in Bratislava, Odbojarov 10, 832 32 Bratislava, SlovakiaDepartment of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Palackeho 1946/1, 612 42 Brno, Czech RepublicDepartment of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech RepublicDepartment of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 61242 Brno, Czech RepublicDepartment of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences in Brno, Palackeho 1946/1, 612 42 Brno, Czech RepublicGlobal Change Research Institute CAS, Belidla 986/4a, 603 00 Brno, Czech RepublicDepartment of Infectious Diseases and Microbiology, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences, Palackeho 1946/1, 612 42 Brno, Czech RepublicRegional Centre of Advanced Technologies and Materials, Faculty of Science, Palacky University, Slechtitelu 27, 783 71 Olomouc, Czech Republic1-[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 <i>Staphylococcus aureus</i> ATCC 29213, <i>Enterococcus faecalis</i> ATCC 29212 (reference and control strains), three methicillin-resistant isolates of <i>S. aureus</i>, and three isolates of vancomycin-resistant <i>E. faecalis</i>. 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. IC<sub>50</sub> values of the most effective compounds ranged from ca. 3.5 to 6.3 µM, 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 <i>S. aureus</i> 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.https://www.mdpi.com/2079-6382/9/2/64carbamateantibacterialsynergyantibiofilm activitystructure–activity relationships |
| spellingShingle | Šárka Pospíšilová Ivan Malík Kristyna Bezouskova Tereza Kauerova Peter Kollar Jozef Csöllei Michal Oravec Alois Cizek Josef Jampilek Dibasic Derivatives of Phenylcarbamic Acid as Prospective Antibacterial Agents Interacting with Cytoplasmic Membrane Antibiotics carbamate antibacterial synergy antibiofilm activity structure–activity relationships |
| title | Dibasic Derivatives of Phenylcarbamic Acid as Prospective Antibacterial Agents Interacting with Cytoplasmic Membrane |
| title_full | Dibasic Derivatives of Phenylcarbamic Acid as Prospective Antibacterial Agents Interacting with Cytoplasmic Membrane |
| title_fullStr | Dibasic Derivatives of Phenylcarbamic Acid as Prospective Antibacterial Agents Interacting with Cytoplasmic Membrane |
| title_full_unstemmed | Dibasic Derivatives of Phenylcarbamic Acid as Prospective Antibacterial Agents Interacting with Cytoplasmic Membrane |
| title_short | Dibasic Derivatives of Phenylcarbamic Acid as Prospective Antibacterial Agents Interacting with Cytoplasmic Membrane |
| title_sort | dibasic derivatives of phenylcarbamic acid as prospective antibacterial agents interacting with cytoplasmic membrane |
| topic | carbamate antibacterial synergy antibiofilm activity structure–activity relationships |
| url | https://www.mdpi.com/2079-6382/9/2/64 |
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