Chiral Pool Synthesis, Biological Evaluation and Molecular Docking Studies of C-Furanosidic LpxC Inhibitors.
ChemMedChem
; 14(8): 871-886, 2019 04 17.
Article
en En
| MEDLINE
| ID: mdl-30801965
ABSTRACT
Inhibitors of the bacterial deacetylase LpxC are a promising class of novel antibiotics, being selectively active against Gram-negative bacteria. To improve the biological activity of reported C-furanosidic LpxC inhibitors, the stereochemistry at positionsâ
3 and 4 of the tetrahydrofuran ring was varied. In chiral pool syntheses starting from d-gulono-γ-lactone and d-ribose, a series of (3S,4R)-configured dihydroxytetrahydrofuran derivatives was obtained, of which the (2S,5S)-configured hydroxamic acid 15 ((2S,3S,4R,5S)-N,3,4-trihydroxy-5-(4-{[4-(morpholinomethyl)phenyl]ethynyl}phenyl)tetrahydrofuran-2-carboxamide) was found to be the most potent LpxC inhibitor (Ki =0.4â
µm), exhibiting the highest antibacterial activity against E.â
coli BL21 (DE3) and the D22 strain. Additionally, molecular docking studies were performed to rationalize the obtained structure-activity relationships.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_neglected_diseases
/
3_zoonosis
Asunto principal:
Proteínas Bacterianas
/
Inhibidores Enzimáticos
/
Simulación del Acoplamiento Molecular
/
Furanos
/
Amidohidrolasas
Idioma:
En
Revista:
ChemMedChem
Asunto de la revista:
FARMACOLOGIA
/
QUIMICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Alemania