Glucoimines incorporating classical and non-classical carbonic anhydrase pharmacophores: Design, synthesis, conformational analysis, biological evaluation, and docking simulations

In this report, a series of glucoimines has been prepared by reaction of d-glucosamine and aromatic aldehydes incorporating classical and non-classical carbonic anhydrase pharmacophores. The conformational behavior of veratrole glucoimine was studied in solution and in crystalline form, by NMR and X...

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Autores principales: Vásquez, Ivana Raquel, Riafrecha, Leonardo Ezequiel, Martínez Heredia, Leandro, Echeverría, Gustavo Alberto, Piro, Oscar Enrique, Lavecchia, Martín José, Supuran, Claudiu T., Colinas, Pedro Alfonso
Formato: Articulo
Lenguaje:Inglés
Publicado: 2024
Materias:
Química
Imines
Cancer
Enzyme inhibitor
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/172520
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-172520
record_format dspace
spelling I19-R120-10915-1725202024-11-04T20:10:36Z http://sedici.unlp.edu.ar/handle/10915/172520 Glucoimines incorporating classical and non-classical carbonic anhydrase pharmacophores: Design, synthesis, conformational analysis, biological evaluation, and docking simulations Vásquez, Ivana Raquel Riafrecha, Leonardo Ezequiel Martínez Heredia, Leandro Echeverría, Gustavo Alberto Piro, Oscar Enrique Lavecchia, Martín José Supuran, Claudiu T. Colinas, Pedro Alfonso 2024-08-28 2024-11-04T16:58:33Z en Química Imines Cancer Enzyme inhibitor In this report, a series of glucoimines has been prepared by reaction of d-glucosamine and aromatic aldehydes incorporating classical and non-classical carbonic anhydrase pharmacophores. The conformational behavior of veratrole glucoimine was studied in solution and in crystalline form, by NMR and X-ray diffraction analysis, which revealed that pyranose ring adopted a 4C1 conformation. All glucoimines were tested against four isozymes of carbonic anhydrase: hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (tumor-associated isozymes). In this study, per-O-acetylated and deprotected sulfonamide were identified as potent inhibitors of tumor-associated carbonic anhydrase isoforms. Molecular docking simulation was performed inside the active site of hCA II to evaluate the binding modes of veratrole and sulfonamide glucoimines. The last ones demonstrated the most favorable docking scores, indicating strong binding affinity towards hCAII in correlation with experimental inhibition activities. Interestingly, interaction analyses revealed distinct binding modes for ligand-hCAII complexes primarily due to the sulfonamide group. Facultad de Ciencias Exactas Centro de Estudios de Compuestos Orgánicos Articulo Articulo http://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International (CC BY 4.0) application/pdf
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Química
Imines
Cancer
Enzyme inhibitor
spellingShingle Química
Imines
Cancer
Enzyme inhibitor
Vásquez, Ivana Raquel
Riafrecha, Leonardo Ezequiel
Martínez Heredia, Leandro
Echeverría, Gustavo Alberto
Piro, Oscar Enrique
Lavecchia, Martín José
Supuran, Claudiu T.
Colinas, Pedro Alfonso
Glucoimines incorporating classical and non-classical carbonic anhydrase pharmacophores: Design, synthesis, conformational analysis, biological evaluation, and docking simulations
topic_facet Química
Imines
Cancer
Enzyme inhibitor
description In this report, a series of glucoimines has been prepared by reaction of d-glucosamine and aromatic aldehydes incorporating classical and non-classical carbonic anhydrase pharmacophores. The conformational behavior of veratrole glucoimine was studied in solution and in crystalline form, by NMR and X-ray diffraction analysis, which revealed that pyranose ring adopted a 4C1 conformation. All glucoimines were tested against four isozymes of carbonic anhydrase: hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (tumor-associated isozymes). In this study, per-O-acetylated and deprotected sulfonamide were identified as potent inhibitors of tumor-associated carbonic anhydrase isoforms. Molecular docking simulation was performed inside the active site of hCA II to evaluate the binding modes of veratrole and sulfonamide glucoimines. The last ones demonstrated the most favorable docking scores, indicating strong binding affinity towards hCAII in correlation with experimental inhibition activities. Interestingly, interaction analyses revealed distinct binding modes for ligand-hCAII complexes primarily due to the sulfonamide group.
format Articulo
Articulo
author Vásquez, Ivana Raquel
Riafrecha, Leonardo Ezequiel
Martínez Heredia, Leandro
Echeverría, Gustavo Alberto
Piro, Oscar Enrique
Lavecchia, Martín José
Supuran, Claudiu T.
Colinas, Pedro Alfonso
author_facet Vásquez, Ivana Raquel
Riafrecha, Leonardo Ezequiel
Martínez Heredia, Leandro
Echeverría, Gustavo Alberto
Piro, Oscar Enrique
Lavecchia, Martín José
Supuran, Claudiu T.
Colinas, Pedro Alfonso
author_sort Vásquez, Ivana Raquel
title Glucoimines incorporating classical and non-classical carbonic anhydrase pharmacophores: Design, synthesis, conformational analysis, biological evaluation, and docking simulations
title_short Glucoimines incorporating classical and non-classical carbonic anhydrase pharmacophores: Design, synthesis, conformational analysis, biological evaluation, and docking simulations
title_full Glucoimines incorporating classical and non-classical carbonic anhydrase pharmacophores: Design, synthesis, conformational analysis, biological evaluation, and docking simulations
title_fullStr Glucoimines incorporating classical and non-classical carbonic anhydrase pharmacophores: Design, synthesis, conformational analysis, biological evaluation, and docking simulations
title_full_unstemmed Glucoimines incorporating classical and non-classical carbonic anhydrase pharmacophores: Design, synthesis, conformational analysis, biological evaluation, and docking simulations
title_sort glucoimines incorporating classical and non-classical carbonic anhydrase pharmacophores: design, synthesis, conformational analysis, biological evaluation, and docking simulations
publishDate 2024
url http://sedici.unlp.edu.ar/handle/10915/172520
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