Synthesis, Antimicrobial Activities, and Molecular Modeling Studies of Agents for the Sortase A Enzyme.
Chem Biodivers
; 21(5): e202301659, 2024 May.
Article
en En
| MEDLINE
| ID: mdl-38407541
ABSTRACT
Sortase A (SrtA) is an attractive target for developing new anti-infective drugs that aim to interfere with essential virulence mechanisms, such as adhesion to host cells and biofilm formation. Herein, twenty hydroxy, nitro, bromo, fluoro, and methoxy substituted chalcone compounds were synthesized, antimicrobial activities and molecular modeling strategies against the SrtA enzyme were investigated. The most active compounds were found to be T2, T4, and T19 against Streptococcus mutans (S. mutans) with MIC values of 1.93, 3.8, 3.94â
µg/mL, and docking scores of -6.46, -6.63, -6.73â
kcal/mol, respectively. Also, these three active compounds showed better activity than the chlorohexidine (CHX) (MIC value 4.88â
µg/mL, docking score -6.29â
kcal/mol) in both inâ
vitro and in silico. Structural stability and binding free energy analysis of S.mutans SrtA with active compounds were measured by molecular dynamic (MD) simulations throughout 100 nanoseconds (ns) time. It was observed that the stability of the critical interactions between these compounds and the target enzyme was preserved. To prove further, inâ
vivo biological evaluation studies could be conducted for the most promising precursor compounds T2, T4, and T19, and it might open new avenues to the discovery of more potent SrtA inhibitors.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Streptococcus mutans
/
Proteínas Bacterianas
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Cisteína Endopeptidasas
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Pruebas de Sensibilidad Microbiana
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Aminoaciltransferasas
Idioma:
En
Revista:
Chem Biodivers
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2024
Tipo del documento:
Article