Bacterial Peptide deformylase inhibition of cyano substituted biaryl analogs: Synthesis, in vitro biological evaluation, molecular docking study and in silico ADME prediction.
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.
Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431001, M.S., India.
Firoz A Kalam
FA
Khan
Department of Biotechnology, Savitribai Phule Pune University, Pune 411007, M.S., India.
Rajendra H
RH
Patil
Shivaji University, Vidyanagar, Kolhapur 416 004, M.S., India.
Devanand B
DB
Shinde
Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431001, M.S., India. Electronic address: jnsangshetti@rediffmail.com.
Jaiprakash N
JN
Sangshetti
D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D013057:Spectrum Analysis / Q000379:methods
D000900:Anti-Bacterial Agents; D000581:Amidohydrolases; C084507:peptide deformylase
ADME properties; Antibacterial activity; Cyano substituted biaryl analogs; Molecular docking; PDF inhibition