Biphenyl tetrazole-thiazolidinediones as novel bacterial peptide deformylase inhibitors: Synthesis, biological evaluations and molecular docking study

Abstract

Herein, we report the synthesis and screening of biphenyl tetrazole-thiazolidinediones 14(a-j) as bacterial Peptide deformylase (PDF) enzyme inhibitors. The compounds 14b (IC50 value = 16.25 mu M), 14c (IC50 value = 18.00 mu M) and 14h (IC50 value = 17.25 mu M) had shown good PDF inhibition activity. The compounds 14b (MIC range = 20.75-35.41 mu g/mL), 14c (MIC range = 19.41-26.00 mu g/mL) and 14d (MIC range = 8.41-8.58 mu g/mL) had also shown potent antibacterial activity when compared with standard ciprofloxacin (MIC range = 25-50 mu g/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 enzyme, the synthesized compounds 14(a-j) were docked against PDF enzyme of E. coli and compounds exhibited good binding properties. The results suggest that this class of compounds have been potential for development and use in a future as antibacterial drugs. (C) 2016 Elsevier Masson SAS. All rights reserved.