TY - JOUR
T1 - Two new fluorinated phenol derivatives pyridine schiff bases
T2 - Synthesis, spectral, theoretical characterization, inclusion in epichlorohydrin-β-cyclodextrin polymer, and antifungal effect
AU - Carreño, Alexander
AU - Rodríguez, Leonardo
AU - Páez-Hernández, Dayán
AU - Martin-Trasanco, Rudy
AU - Zúñiga, César
AU - Oyarzún, Diego P.
AU - Gacitúa, Manuel
AU - Schott, Eduardo
AU - Arratia-Pérez, Ramiro
AU - Fuentes, Juan A.
N1 - Publisher Copyright:
© 2018 Carreño, Rodríguez, Páez-Hernández, Martin-Trasanco, Zúñiga, Oyarzún, Gacitúa, Schott, Arratia-Pérez and Fuentes.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Antifungal agents
KW - Cryptococcus
KW - DFT calculations
KW - Epichlorohydrin-β-cyclodextrin polymer
KW - Intramolecular hydrogen bonds
KW - Schiff base
UR - http://www.scopus.com/inward/record.url?scp=85053079857&partnerID=8YFLogxK
U2 - 10.3389/fchem.2018.00312
DO - 10.3389/fchem.2018.00312
M3 - Article
AN - SCOPUS:85053079857
SN - 2296-2646
VL - 6
JO - Frontiers in Chemistry
JF - Frontiers in Chemistry
IS - JUL
M1 - 312
ER -