Two new fluorinated phenol derivatives pyridine schiff bases

Synthesis, spectral, theoretical characterization, inclusion in epichlorohydrin-β-cyclodextrin polymer, and antifungal effect

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number312
JournalFrontiers in Chemistry
Volume6
Issue numberJUL
DOIs
Publication statusPublished - 1 Jan 2018

Fingerprint

Schiff Bases
Phenol
Fluorine
Derivatives
Substitution reactions
Solubility
Dimethyl Sulfoxide
Bioactivity
Discrete Fourier transforms
Yeast
Cyclic voltammetry
Polymers
Nitrogen
Nuclear magnetic resonance
cyclodextrin-epichlorohydrin polymer
pyridine
Pharmaceutical Preparations

Keywords

  • Antifungal agents
  • Cryptococcus
  • DFT calculations
  • Epichlorohydrin-β-cyclodextrin polymer
  • Intramolecular hydrogen bonds
  • Schiff base

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

@article{cac7e93ca9e2406da71f84c9ba90e80a,
title = "Two new fluorinated phenol derivatives pyridine schiff bases: Synthesis, spectral, theoretical characterization, inclusion in epichlorohydrin-β-cyclodextrin polymer, and antifungal effect",
abstract = "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.",
keywords = "Antifungal agents, Cryptococcus, DFT calculations, Epichlorohydrin-β-cyclodextrin polymer, Intramolecular hydrogen bonds, Schiff base",
author = "Alexander Carre{\~n}o and Leonardo Rodr{\'i}guez and Day{\'a}n P{\'a}ez-Hern{\'a}ndez and Rudy Martin-Trasanco and C{\'e}sar Z{\'u}{\~n}iga and Oyarz{\'u}n, {Diego P.} and Manuel Gacit{\'u}a and Eduardo Schott and Ramiro Arratia-P{\'e}rez and Fuentes, {Juan A.}",
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language = "English",
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Two new fluorinated phenol derivatives pyridine schiff bases : Synthesis, spectral, theoretical characterization, inclusion in epichlorohydrin-β-cyclodextrin polymer, and antifungal effect. / Carreño, Alexander; Rodríguez, Leonardo; Páez-Hernández, Dayán; Martin-Trasanco, Rudy; Zúñiga, César; Oyarzún, Diego P.; Gacitúa, Manuel; Schott, Eduardo; Arratia-Pérez, Ramiro; Fuentes, Juan A.

In: Frontiers in Chemistry, Vol. 6, No. JUL, 312, 01.01.2018.

Research output: Contribution to journalArticle

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.

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

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U2 - 10.3389/fchem.2018.00312

DO - 10.3389/fchem.2018.00312

M3 - Article

VL - 6

JO - Frontiers in Chemistry

JF - Frontiers in Chemistry

SN - 2296-2646

IS - JUL

M1 - 312

ER -