Bacterial Peptide deformylase inhibition of cyano substituted biaryl analogs: Synthesis, in vitro biological evaluation, molecular docking study and in silico ADME prediction.
Bioorg Med Chem
; 24(16): 3456-63, 2016 08 15.
Article
em En
| MEDLINE
| ID: mdl-27269198
ABSTRACT
Herein, we report the synthesis and screening of cyano substituted biaryl analogs 5(a-m) as Peptide deformylase (PDF) enzyme inhibitors. The compounds 5a (IC50 value=13.16µM), 5d (IC50 value=15.66µM) and 5j (IC50 value=19.16µM) had shown good PDF inhibition activity. The compounds 5a (MIC range=11.00-15.83µg/mL), 5b (MIC range=23.75-28.50µg/mL) and 5j (MIC range=7.66-16.91µg/mL) had also shown potent antibacterial activity when compared with ciprofloxacin (MIC range=25-50µg/mL). Thus, the active derivatives were not only potent PDF inhibitors but also efficient antibacterial agents. In order to gain more insight on the binding mode of the compounds with PDF, the synthesized compounds 5(a-m) were docked against PDF enzyme of Escherichia coli and compounds exhibited good binding properties. In silico ADME properties of synthesized compounds were also analyzed and showed potential to develop as good oral drug candidates.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Amidoidrolases
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article