Phenylalanine and Tryptophan-Based Surfactants as New Antibacterial Agents: Characterization, Self-Aggregation Properties, and DPPC/Surfactants Vesicles Formulation
Cationic surfactants based on phenylalanine (C<sub>n</sub>PC<sub>3</sub>NH<sub>3</sub>Cl) and tryptophan (C<sub>n</sub>TC<sub>3</sub>NH<sub>3</sub>Cl) were synthesized using renewable raw materials as starting compounds and a gr...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/7/1856 |
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| author | Zakaria Hafidi Lourdes Pérez Mohammed El Achouri Ramon Pons |
| author_facet | Zakaria Hafidi Lourdes Pérez Mohammed El Achouri Ramon Pons |
| author_sort | Zakaria Hafidi |
| collection | DOAJ |
| description | Cationic surfactants based on phenylalanine (C<sub>n</sub>PC<sub>3</sub>NH<sub>3</sub>Cl) and tryptophan (C<sub>n</sub>TC<sub>3</sub>NH<sub>3</sub>Cl) were synthesized using renewable raw materials as starting compounds and a green synthetic procedure. The synthesis, acid-base equilibrium, aggregation properties, and antibacterial activity were investigated. Conductivity and fluorescence were used to establish critical micelle concentrations. Micellization of C<sub>n</sub>PC<sub>3</sub>NH<sub>3</sub>Cl and C<sub>n</sub>TC<sub>3</sub>NH<sub>3</sub>Cl occurred in the ranges of 0.42–16.2 mM and 0.29–4.6 mM, respectively. Since those surfactants have some acidic character, the apparent pK<sub>a</sub> was determined through titrations, observing increasing acidity with increasing chain length and being slightly more acidic with the phenylalanine than the tryptophan derivatives. Both families showed promising antibacterial efficacy against eight different bacterial strains. Molecular docking studies against the enzyme peptidoglycan glycosyltransferase (PDB ID:2OQO) were used to investigate the potential binding mechanism of target surfactant molecules. According to small angle X-ray scattering (SAXS) results, the surfactants incorporate into DPPC (Dipalmitoyl Phosphatidyl Choline) bilayers without strong perturbation up to high surfactant concentration. Some of the C<sub>12</sub>TC<sub>3</sub>NH<sub>3</sub>Cl/DPPC formulations (40%/60% and 20%/80% molar ratios) exhibited good antibacterial activity, while the others were not effective against the tested bacteria. The strong affinity between DPPC and surfactant molecules, as determined by the DFT (density functional theory) method, could be one of the reasons for the loss of antibacterial activity of these cationic surfactants when they are incorporated in vesicles. |
| first_indexed | 2024-03-11T00:43:42Z |
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| id | doaj.art-25942d12877b46fcae1928fd5f51478f |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T00:43:42Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-25942d12877b46fcae1928fd5f51478f2023-11-18T20:54:48ZengMDPI AGPharmaceutics1999-49232023-06-01157185610.3390/pharmaceutics15071856Phenylalanine and Tryptophan-Based Surfactants as New Antibacterial Agents: Characterization, Self-Aggregation Properties, and DPPC/Surfactants Vesicles FormulationZakaria Hafidi0Lourdes Pérez1Mohammed El Achouri2Ramon Pons3Department of Surfactants and Nanobiotechnology, IQAC-CSIC, 08034 Barcelona, SpainDepartment of Surfactants and Nanobiotechnology, IQAC-CSIC, 08034 Barcelona, SpainLaboratoire de Physico-Chimie des Matériaux Inorganiques et Organiques, Centre des Sciences des Matériaux, Ecole Normale Supérieure-Rabat, Mohammed V Université in Rabat, Rabat 5118, MoroccoDepartment of Surfactants and Nanobiotechnology, IQAC-CSIC, 08034 Barcelona, SpainCationic surfactants based on phenylalanine (C<sub>n</sub>PC<sub>3</sub>NH<sub>3</sub>Cl) and tryptophan (C<sub>n</sub>TC<sub>3</sub>NH<sub>3</sub>Cl) were synthesized using renewable raw materials as starting compounds and a green synthetic procedure. The synthesis, acid-base equilibrium, aggregation properties, and antibacterial activity were investigated. Conductivity and fluorescence were used to establish critical micelle concentrations. Micellization of C<sub>n</sub>PC<sub>3</sub>NH<sub>3</sub>Cl and C<sub>n</sub>TC<sub>3</sub>NH<sub>3</sub>Cl occurred in the ranges of 0.42–16.2 mM and 0.29–4.6 mM, respectively. Since those surfactants have some acidic character, the apparent pK<sub>a</sub> was determined through titrations, observing increasing acidity with increasing chain length and being slightly more acidic with the phenylalanine than the tryptophan derivatives. Both families showed promising antibacterial efficacy against eight different bacterial strains. Molecular docking studies against the enzyme peptidoglycan glycosyltransferase (PDB ID:2OQO) were used to investigate the potential binding mechanism of target surfactant molecules. According to small angle X-ray scattering (SAXS) results, the surfactants incorporate into DPPC (Dipalmitoyl Phosphatidyl Choline) bilayers without strong perturbation up to high surfactant concentration. Some of the C<sub>12</sub>TC<sub>3</sub>NH<sub>3</sub>Cl/DPPC formulations (40%/60% and 20%/80% molar ratios) exhibited good antibacterial activity, while the others were not effective against the tested bacteria. The strong affinity between DPPC and surfactant molecules, as determined by the DFT (density functional theory) method, could be one of the reasons for the loss of antibacterial activity of these cationic surfactants when they are incorporated in vesicles.https://www.mdpi.com/1999-4923/15/7/1856phenylalanine tryptophansurfactantsantimicrobial activityvesiclesSAXS |
| spellingShingle | Zakaria Hafidi Lourdes Pérez Mohammed El Achouri Ramon Pons Phenylalanine and Tryptophan-Based Surfactants as New Antibacterial Agents: Characterization, Self-Aggregation Properties, and DPPC/Surfactants Vesicles Formulation Pharmaceutics phenylalanine tryptophan surfactants antimicrobial activity vesicles SAXS |
| title | Phenylalanine and Tryptophan-Based Surfactants as New Antibacterial Agents: Characterization, Self-Aggregation Properties, and DPPC/Surfactants Vesicles Formulation |
| title_full | Phenylalanine and Tryptophan-Based Surfactants as New Antibacterial Agents: Characterization, Self-Aggregation Properties, and DPPC/Surfactants Vesicles Formulation |
| title_fullStr | Phenylalanine and Tryptophan-Based Surfactants as New Antibacterial Agents: Characterization, Self-Aggregation Properties, and DPPC/Surfactants Vesicles Formulation |
| title_full_unstemmed | Phenylalanine and Tryptophan-Based Surfactants as New Antibacterial Agents: Characterization, Self-Aggregation Properties, and DPPC/Surfactants Vesicles Formulation |
| title_short | Phenylalanine and Tryptophan-Based Surfactants as New Antibacterial Agents: Characterization, Self-Aggregation Properties, and DPPC/Surfactants Vesicles Formulation |
| title_sort | phenylalanine and tryptophan based surfactants as new antibacterial agents characterization self aggregation properties and dppc surfactants vesicles formulation |
| topic | phenylalanine tryptophan surfactants antimicrobial activity vesicles SAXS |
| url | https://www.mdpi.com/1999-4923/15/7/1856 |
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