Water-assisted cascade synthesis of trifluoromethylated dipyridodiazepinone analogues: in vitro and in silico antibacterial studies.
Org Biomol Chem
; 22(32): 6520-6531, 2024 08 14.
Article
en En
| MEDLINE
| ID: mdl-39072429
ABSTRACT
A base-promoted palladium-catalyzed cascade reaction is described to access trifluoromethylated dipyridodiazepinone derivatives in an aqueous system (1,4-dioxane-H2O). This methodology uses simple chemicals, has a broad substrate scope, is waste minimized (E-factor = 0.3-0.9) and produces 11-CF3-tethered dipyridiodiazepinone derivatives in good to excellent yields. All the synthesized analogues were preliminarily examined for antibacterial activity against E. coli and S. aureus and compared to the reference drugs. Furthermore, inhibition of the peptide deformylase enzyme and antibiofilm studies were performed and compound 5i exhibited the best inhibitory effect among the other analogues. Furthermore, these analogues were in silico analysed via molecular docking, molecular simulation, drug-likeness, physicochemical and ADMET studies. Results from biological evaluation and computational studies revealed that compound 5i could be used as a lead molecular structure for the development of novel antibacterial agents. In conclusion, the green metrics evaluation of the defined protocol provides advantages in the synthesis of biologically active compounds.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Staphylococcus aureus
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Agua
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Pruebas de Sensibilidad Microbiana
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Escherichia coli
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Simulación del Acoplamiento Molecular
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Antibacterianos
Idioma:
En
Revista:
Org Biomol Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
India