Design and synthesis of 4'-((5-benzylidene-2,4-dioxothiazolidin-3-yl)methyl)biphenyl-2-carbonitrile analogs as bacterial peptide deformylase inhibitors.

Abstract

Herein, we report the synthesis and screening of 4'-((5-benzylidene-2,4-dioxothiazolidin-3-yl)methyl)biphenyl-2-carbonitrile analogs 11(a-j) as bacterial peptide deformylase (PDF) enzyme inhibitors. The compounds 11b (IC50 value=139.28μm), 11g (IC50 value=136.18μm), and 11h (IC50 value=131.65μm) had shown good PDF inhibition activity. The compounds 11b (MIC range=103.36-167.26μg/mL), 11g (MIC range=93.75-145.67μg/mL), and 11h (MIC range=63.61-126.63μg/mL) had also shown potent antibacterial activity when compared with standard ampicillin (MIC range=100.00-250.00μg/mL). Thus, the active derivatives were not only PDF inhibitors but also efficient antibacterial agents. To gain more insight on the binding mode of the compounds with PDF enzyme, the synthesized compounds 11(a-j) were docked against PDF enzyme of Escherichia coli and compounds exhibited good binding properties. The results suggest that this class of compounds has potential for development and use in future as antibacterial drugs.