Artículo
Glucoimines incorporating classical and non-classical carbonic anhydrase pharmacophores: Design, synthesis, conformational analysis, biological evaluation, and docking simulations
Vasquez, Ivana Raquel
; Riafrecha, Leonardo Ezequiel
; Martinez Heredia, Leandro
; Echeverría, Gustavo Alberto
; Piro, Oscar Enrique
; Lavecchia, Martín José
; Supuran, Claudiu T.; Colinas, Pedro Alfonso
Fecha de publicación:
08/2024
Editorial:
Elsevier Science
Revista:
Journal of Molecular Structure
ISSN:
0022-2860
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
glucoimines
,
enzyme inhibitor
,
docking
,
X-ray
Archivos asociados
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Identificadores
Colecciones
Articulos(CCT - LA PLATA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - LA PLATA
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - LA PLATA
Articulos(CEQUINOR)
Articulos de CENTRO DE QUIMICA INORGANICA "DR. PEDRO J. AYMONINO"
Articulos de CENTRO DE QUIMICA INORGANICA "DR. PEDRO J. AYMONINO"
Articulos(IFLP)
Articulos de INST.DE FISICA LA PLATA
Articulos de INST.DE FISICA LA PLATA
Citación
Vasquez, Ivana Raquel; Riafrecha, Leonardo Ezequiel; Martinez Heredia, Leandro; Echeverría, Gustavo Alberto; Piro, Oscar Enrique; et al.; Glucoimines incorporating classical and non-classical carbonic anhydrase pharmacophores: Design, synthesis, conformational analysis, biological evaluation, and docking simulations; Elsevier Science; Journal of Molecular Structure; 1321; 8-2024; 1-8
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