Two New Fluorinated Phenol Derivatives Pyridine Schiff Bases: Synthesis, Spectral, Theoretical Characterization, Inclusion in Epichlorohydrin-β-Cyclodextrin Polymer, and Antifungal Effect
It has been reported that the structure of the Schiff bases is fundamental for their function in biomedical applications. Pyridine Schiff bases are characterized by the presence of a pyridine and a phenolic ring, connected by an azomethine group. In this case, the nitrogen present in the pyridine is...
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Frontiers Media S.A.
2018-07-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fchem.2018.00312/full |
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| author | Alexander Carreño Alexander Carreño Leonardo Rodríguez Dayán Páez-Hernández Rudy Martin-Trasanco César Zúñiga Diego P. Oyarzún Manuel Gacitúa Eduardo Schott Ramiro Arratia-Pérez Juan A. Fuentes |
| author_facet | Alexander Carreño Alexander Carreño Leonardo Rodríguez Dayán Páez-Hernández Rudy Martin-Trasanco César Zúñiga Diego P. Oyarzún Manuel Gacitúa Eduardo Schott Ramiro Arratia-Pérez Juan A. Fuentes |
| author_sort | Alexander Carreño |
| collection | DOAJ |
| description | It has been reported that the structure of the Schiff bases is fundamental for their function in biomedical applications. Pyridine Schiff bases are characterized by the presence of a pyridine and a phenolic ring, connected by an azomethine group. In this case, the nitrogen present in the pyridine is responsible for antifungal effects, where the phenolic ring may be also participating in this bioactivity. In this study, we synthesized two new pyridine Schiff Bases: (E)-2-[(3-Amino-pyridin-4-ylimino)-methyl]-4,6-difluoro-phenol (F1) and (E)- 2-[(3-Amino-pyridin-4-ylimino)-methyl]-6-fluoro-phenol (F2), which only differ in the fluorine substitutions in the phenolic ring. We fully characterized both F1 and F2 by FTIR, UV-vis, 1H; 13C; 19F-NMR, DEPT, HHCOSY, TOCSY, and cyclic voltammetry, as well as by computational studies (DFT), and NBO analysis. In addition, we assessed the antifungal activity of both F1 (two fluorine substitution at positions 4 and 6 in the phenolic ring) and F2 (one fluorine substitution at position 6 in the phenolic ring) against yeasts. We found that only F1 exerted a clear antifungal activity, showing that, for these kind of Schiff bases, the phenolic ring substitutions can modulate biological properties. In addition, we included F1 and F2 into in epichlorohydrin-β-cyclodextrin polymer (βCD), where the Schiff bases remained inside the βCD as determined by the ki, TGA, DSC, and SBET. We found that the inclusion in βCD improved the solubility in aqueous media and the antifungal activity of both F1 and F2, revealing antimicrobial effects normally hidden by the presence of common solvents (e.g., DMSO) with some cellular inhibitory activity. The study of structural prerequisites for antimicrobial activity, and the inclusion in polymers to improve solubility, is important for the design of new drugs. |
| first_indexed | 2024-12-14T09:17:10Z |
| format | Article |
| id | doaj.art-7ea36a4df8224f7dbd306f1fd3d3ce32 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-14T09:17:10Z |
| publishDate | 2018-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-7ea36a4df8224f7dbd306f1fd3d3ce322022-12-21T23:08:25ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462018-07-01610.3389/fchem.2018.00312397895Two New Fluorinated Phenol Derivatives Pyridine Schiff Bases: Synthesis, Spectral, Theoretical Characterization, Inclusion in Epichlorohydrin-β-Cyclodextrin Polymer, and Antifungal EffectAlexander Carreño0Alexander Carreño1Leonardo Rodríguez2Dayán Páez-Hernández3Rudy Martin-Trasanco4César Zúñiga5Diego P. Oyarzún6Manuel Gacitúa7Eduardo Schott8Ramiro Arratia-Pérez9Juan A. Fuentes10Center of Applied Nanosciences, Universidad Andres Bello, Santiago, ChileFondo Nacional de Desarrollo Científico y Tecnológico, Santiago, ChileLaboratorio de Genética y Patogénesis Bacteriana, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, ChileCenter of Applied Nanosciences, Universidad Andres Bello, Santiago, ChileCenter of Applied Nanosciences, Universidad Andres Bello, Santiago, ChileCenter of Applied Nanosciences, Universidad Andres Bello, Santiago, ChileCenter of Applied Nanosciences, Universidad Andres Bello, Santiago, ChileFacultad de Química y Biología, USACH, Santiago, ChileDepartamento de Química Inorgánica, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago, ChileCenter of Applied Nanosciences, Universidad Andres Bello, Santiago, ChileLaboratorio de Genética y Patogénesis Bacteriana, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, ChileIt has been reported that the structure of the Schiff bases is fundamental for their function in biomedical applications. Pyridine Schiff bases are characterized by the presence of a pyridine and a phenolic ring, connected by an azomethine group. In this case, the nitrogen present in the pyridine is responsible for antifungal effects, where the phenolic ring may be also participating in this bioactivity. In this study, we synthesized two new pyridine Schiff Bases: (E)-2-[(3-Amino-pyridin-4-ylimino)-methyl]-4,6-difluoro-phenol (F1) and (E)- 2-[(3-Amino-pyridin-4-ylimino)-methyl]-6-fluoro-phenol (F2), which only differ in the fluorine substitutions in the phenolic ring. We fully characterized both F1 and F2 by FTIR, UV-vis, 1H; 13C; 19F-NMR, DEPT, HHCOSY, TOCSY, and cyclic voltammetry, as well as by computational studies (DFT), and NBO analysis. In addition, we assessed the antifungal activity of both F1 (two fluorine substitution at positions 4 and 6 in the phenolic ring) and F2 (one fluorine substitution at position 6 in the phenolic ring) against yeasts. We found that only F1 exerted a clear antifungal activity, showing that, for these kind of Schiff bases, the phenolic ring substitutions can modulate biological properties. In addition, we included F1 and F2 into in epichlorohydrin-β-cyclodextrin polymer (βCD), where the Schiff bases remained inside the βCD as determined by the ki, TGA, DSC, and SBET. We found that the inclusion in βCD improved the solubility in aqueous media and the antifungal activity of both F1 and F2, revealing antimicrobial effects normally hidden by the presence of common solvents (e.g., DMSO) with some cellular inhibitory activity. The study of structural prerequisites for antimicrobial activity, and the inclusion in polymers to improve solubility, is important for the design of new drugs.https://www.frontiersin.org/article/10.3389/fchem.2018.00312/fullschiff baseintramolecular hydrogen bondsDFT calculationsepichlorohydrin-β-cyclodextrin polymerantifungal agentsCryptococcus |
| spellingShingle | Alexander Carreño Alexander Carreño Leonardo Rodríguez Dayán Páez-Hernández Rudy Martin-Trasanco César Zúñiga Diego P. Oyarzún Manuel Gacitúa Eduardo Schott Ramiro Arratia-Pérez Juan A. Fuentes Two New Fluorinated Phenol Derivatives Pyridine Schiff Bases: Synthesis, Spectral, Theoretical Characterization, Inclusion in Epichlorohydrin-β-Cyclodextrin Polymer, and Antifungal Effect Frontiers in Chemistry schiff base intramolecular hydrogen bonds DFT calculations epichlorohydrin-β-cyclodextrin polymer antifungal agents Cryptococcus |
| title | Two New Fluorinated Phenol Derivatives Pyridine Schiff Bases: Synthesis, Spectral, Theoretical Characterization, Inclusion in Epichlorohydrin-β-Cyclodextrin Polymer, and Antifungal Effect |
| title_full | Two New Fluorinated Phenol Derivatives Pyridine Schiff Bases: Synthesis, Spectral, Theoretical Characterization, Inclusion in Epichlorohydrin-β-Cyclodextrin Polymer, and Antifungal Effect |
| title_fullStr | Two New Fluorinated Phenol Derivatives Pyridine Schiff Bases: Synthesis, Spectral, Theoretical Characterization, Inclusion in Epichlorohydrin-β-Cyclodextrin Polymer, and Antifungal Effect |
| title_full_unstemmed | Two New Fluorinated Phenol Derivatives Pyridine Schiff Bases: Synthesis, Spectral, Theoretical Characterization, Inclusion in Epichlorohydrin-β-Cyclodextrin Polymer, and Antifungal Effect |
| title_short | Two New Fluorinated Phenol Derivatives Pyridine Schiff Bases: Synthesis, Spectral, Theoretical Characterization, Inclusion in Epichlorohydrin-β-Cyclodextrin Polymer, and Antifungal Effect |
| title_sort | two new fluorinated phenol derivatives pyridine schiff bases synthesis spectral theoretical characterization inclusion in epichlorohydrin β cyclodextrin polymer and antifungal effect |
| topic | schiff base intramolecular hydrogen bonds DFT calculations epichlorohydrin-β-cyclodextrin polymer antifungal agents Cryptococcus |
| url | https://www.frontiersin.org/article/10.3389/fchem.2018.00312/full |
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