Efficacy of Novel Quaternary Ammonium and Phosphonium Salts Differing in Cation Type and Alkyl Chain Length against Antibiotic-Resistant Staphylococcus aureus
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemical Studies
2.1.1. Synthesis of Quaternary Ammonium and Phosphonium Salts
2.1.2. Determination of the Chromatographic Hydrophobicity Index
2.2. Microbiological Studies
2.2.1. Determination of Inhibitory/Bactericidal Activities of Quaternary Ammonium and Phosphonium Salts against an Antibiotic-Susceptible S. aureus Strain: Structure–Activity Relationship Analyses
2.2.2. Determination of Inhibitory/Bactericidal Activities of the Most Promising Quaternary Ammonium and Phosphonium Salts against Antibiotic-Resistant S. aureus Strains
2.2.3. Quaternary Ammonium and Phosphonium Salts Activity against Planktonic Bacteria: Dose–Response
2.3. Cytotoxicity Cell-Based Studies
Evaluation of the Cytotoxicity Profile in Human Hepatocellular Carcinoma Cells
3. Materials and Methods
3.1. Chemical Studies
3.1.1. Reagents and Apparatus
3.1.2. Chemical Synthesis and Structural Characterization
Synthesis of Triphenylphosphonium, Methylimidazolium, Isoquinolinium, Methylpyridinium, Quinolinium, and Pyridinium Salts
Synthesis of Triethylammonium Salts
3.1.3. Evaluation of the Chromatographic Hydrophobicity Index
3.2. Microbiological Studies
3.2.1. Preparation of the Quaternary Ammonium and Phosphonium Salts
3.2.2. Bacterial Strains and Culture Conditions
3.2.3. Evaluation of Minimum Inhibitory Concentration and Minimum Bactericidal Concentration
3.2.4. Antimicrobial Susceptibility Test: Dose–Response
3.3. Cytotoxicity Cell-Based Studies
3.3.1. Reagents and Solvents
3.3.2. Preparation of the Quaternary Ammonium and Phosphonium Salts
3.3.3. Cell Culture and Conditions
3.3.4. Evaluation of the Cytotoxicity
3.3.5. Data Analysis and Statistics
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound | tR/min | CHI 1 | CHI LogP 2 |
---|---|---|---|
1a | 6.599 | 60.58 | 1.747 |
1b | 7.096 | 71.06 | 2.240 |
1c | 7.642 | 82.58 | 2.781 |
1d | 8.207 | 94.50 | 3.341 |
1e | 8.706 | 105.0 | 3.836 |
1f | 9.202 | 115.5 | 4.328 |
1g | 9.806 | 128.2 | 4.926 |
2a | 5.118 | 29.35 | 0.2794 |
2b | 5.727 | 42.19 | 0.8830 |
2c | 6.311 | 54.51 | 1.462 |
2d | 6.915 | 67.25 | 2.061 |
2e | 7.584 | 81.36 | 2.724 |
2f | 8.274 | 95.91 | 3.408 |
2g | 8.906 | 109.2 | 4.034 |
3a | 5.519 | 37.81 | 0.6769 |
3b | 6.098 | 50.02 | 1.251 |
3c | 6.648 | 61.62 | 1.796 |
3d | 7.258 | 74.48 | 2.401 |
3e | 7.898 | 87.98 | 3.035 |
3f | 8.508 | 100.8 | 3.640 |
3g | 9.087 | 113.1 | 4.214 |
4a | 5.200 | 31.08 | 0.3607 |
4b | 5.808 | 43.90 | 0.9633 |
4c | 6.381 | 55.99 | 1.531 |
4d | 6.996 | 68.96 | 2.141 |
4e | 7.657 | 82.90 | 2.796 |
4f | 8.315 | 96.77 | 3.448 |
4g | 8.902 | 109.2 | 4.030 |
5a | 5.480 | 36.98 | 0.6382 |
5b | 6.061 | 49.24 | 1.214 |
5c | 6.640 | 61.45 | 1.788 |
5d | 7.245 | 74.21 | 2.388 |
5e | 7.899 | 88.00 | 3.036 |
5f | 8.519 | 101.1 | 3.651 |
5g | 9.081 | 112.9 | 4.208 |
6a | 5.010 | 27.07 | 0.1723 |
6b | 5.660 | 40.78 | 0.8166 |
6c | 6.243 | 53.07 | 1.395 |
6d | 6.836 | 65.58 | 1.982 |
6e | 7.515 | 79.90 | 2.655 |
6f | 8.206 | 94.47 | 3.340 |
6g | 8.853 | 108.1 | 3.982 |
Compound | CECT 976 | |
---|---|---|
MIC 1 | MBC 2 | |
1a | 8 | >64 |
1b | 2 | 16 |
1c | 1 | 8 |
1d | 1 | 16 |
1e | 1 | 16 |
1f | 2 | 16 |
1g | 4 | 64 |
2a | >64 | >64 |
2b | >64 | >64 |
2c | 16 | >64 |
2d | 1 | 16 |
2e | 1 | 8 |
2f | 4 | 8 |
2g | 8 | 16 |
3a | >64 | >64 |
3b | 64 | >64 |
3c | 16 | 64 |
3d | 2 | 16 |
3e | 2 | 8 |
3f | 4 | 8 |
3g | 8 | 16 |
4a | >64 | >64 |
4b | >64 | >64 |
4c | 32 | >64 |
4d | 2 | 16 |
4e | 2 | 8 |
4f | 4 | 8 |
4g | 8 | 16 |
5a | >64 | >64 |
5b | 16 | >64 |
5c | 16 | 32 |
5d | 4 | 16 |
5e | 2 | 8 |
5f | 4 | 8 |
5g | 16 | 16 |
6a | >64 | >64 |
6b | >64 | >64 |
6c | 32 | >64 |
6d | 2 | 8 |
6e | 4 | 8 |
6f | 4 | 8 |
6g | 8 | 16 |
7a | >64 | >64 |
7b | >64 | >64 |
7c | 64 | >64 |
7d | 4 | 16 |
7e | 2 | 16 |
7f | 64 | 64 |
7g | 16 | 16 |
[ERY] | 0.24 | ND |
[TET] | 0.96 | ND |
[CIP] | 1 | ND |
[AMP] | 1.5 | ND |
[OXA] | 0.48 | ND |
Compound | XU212 | SA1199B | RN4220 | |||
---|---|---|---|---|---|---|
MIC 1 | MBC 2 | MIC 1 | MBC 2 | MIC 1 | MBC 2 | |
1e | 2 | 2 | 1 | 2 | 1 | 2 |
2e | 32 | 64 | 8 | 32 | 4 | 8 |
3e | 4 | 8 | 2 | 8 | 2 | 4 |
4e | 32 | 32 | 8 | 32 | 4 | 8 |
5e | 8 | 8 | 4 | 8 | 2 | 8 |
6e | 32 | 64 | 16 | 16 | 4 | 8 |
7e | 32 | 32 | 16 | 32 | 4 | 8 |
[ERY] | ND | ND | ND | ND | 256 | ND |
[TET] | 128 | ND | ND | ND | ND | ND |
[CIP] | ND | ND | 128 | ND | ND | ND |
Compound | Concentration (µg/mL) | |||
---|---|---|---|---|
1 | 2 | 16 | 32 | |
1e | 53.86 ± 4.854% (****) | 72.84 ± 7.906% (****) | 12.29 ± 3.775% (****) | 13.78 ± 2.666% (****) |
2e | 90.88 ± 10.08% (**) | 86.71 ± 4.103% (****) | 12.85 ± 2.005% (****) | 13.64 ± 2.776% (****) |
3e | ND | 79.86 ± 9.893% (****) | 12.68 ± 2.385% (****) | 12.77 ± 1.368% (****) |
4e | ND | 92.62 ± 4.355% (*) | 14.45 ± 2.437% (****) | 21.52 ± 19.06% (****) |
5e | ND | 88.20 ± 3.101% (****) | 12.06 ± 2.988% (****) | 14.38 ± 4.045% (****) |
6e | ND | 94.21 ± 10.35% (ns) | 10.46 ± 3.129% (****) | 12.93 ± 3.760% (****) |
7e | ND | 86.24 ± 1.502% (****) | 18.51 ± 2.592% (****) | 16.59 ± 4.378% (****) |
[ERY] | ND | 108.4 ± 4.998% (ns) | 107.1 ± 7.642% (ns) | 110.2 ± 9.546% (ns) |
[TET] | ND | 109.0 ± 5.251% (ns) | 107.5 ± 9.694% (ns) | 106.8 ± 6.699% (ns) |
[CIP] | ND | 106.7 ± 11.16% (ns) | 96.82 ± 5.237% (ns) | 92.35 ± 6.807% (ns) |
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Nunes, B.; Cagide, F.; Fernandes, C.; Borges, A.; Borges, F.; Simões, M. Efficacy of Novel Quaternary Ammonium and Phosphonium Salts Differing in Cation Type and Alkyl Chain Length against Antibiotic-Resistant Staphylococcus aureus. Int. J. Mol. Sci. 2024, 25, 504. https://doi.org/10.3390/ijms25010504
Nunes B, Cagide F, Fernandes C, Borges A, Borges F, Simões M. Efficacy of Novel Quaternary Ammonium and Phosphonium Salts Differing in Cation Type and Alkyl Chain Length against Antibiotic-Resistant Staphylococcus aureus. International Journal of Molecular Sciences. 2024; 25(1):504. https://doi.org/10.3390/ijms25010504
Chicago/Turabian StyleNunes, Bárbara, Fernando Cagide, Carlos Fernandes, Anabela Borges, Fernanda Borges, and Manuel Simões. 2024. "Efficacy of Novel Quaternary Ammonium and Phosphonium Salts Differing in Cation Type and Alkyl Chain Length against Antibiotic-Resistant Staphylococcus aureus" International Journal of Molecular Sciences 25, no. 1: 504. https://doi.org/10.3390/ijms25010504