Synthesis Of 2,5-dihydropyrrole Formyl Hydroxyamino Derivatives As Novel Peptide Deformalase Inhibitor

Peptide deformylase (PDF), a highly onserved metalloproteinase, is an essential enzyme in the bacterial life cycle. It catalyses the remlval of the N-terminal formaly group from the N-terminal methionine during bacterial protein synthesis, but it is not required by mammalian cells. Therefore, PDF is one of the most impressive targets. The peptide deformylase is able to kill the bacteria selectively without interfering normal cell, antibiotics based on PDF inhibition have the potential to provide the much needed antibacterial activity against most of the major drug-resistant pathogens.LBM-415 is one of the peptide deformylase inhibitors which has entered clinical evolution, research indicates it has notable activity to many pathogenic bacteria. According to the structure-activity relationship (SAR) of peptide defor-mylase inhibitors, A kind of 2,5-dihydropyrrole formyl hydroxyamino derivatives were synthesized as novel PDF inhibitors based on the structure of LBM-415, and their in vitro antibacterial activities were evaluated. The new kind peptide deformylase inhibitor including 2,5-dihydropyrrole structure displayed equal even higher in vitro antibacterial activities than LBM415, and showed better in vitro antibacterial activities than existing drugs including vancomycin, linezolid, and the latter are primary means for inhibting antibiotic-resistant bacteria in nowdays.We synthesized a new kind peptide deformylase inhibitor including 2,5-dihydro pyrrole structure, and their in vitro antibacterial activities were evaluated, showing good results, is expected to develop into a new kind antibiotics against ntibiotic-resistant bacteria.