Synthesis and anti-Helicobacter pylori activity of pyloricidin derivatives -: I.: Structure-activity relationships on the terminal peptidic moiety

The novel natural antibiotics pyloricidin A, B and C possess potent and highly selective antibacterial activity against Helicobacter pylori. In order to investigate the structure activity relationships for the terminal peptidic moiety, a series of pyloricidin B and pyloricidin C derivatives, bearing various amino acids in the moiety, were prepared and evaluated for their anti-H. pylori activity. The derivatives bearing alpha-D-, beta- and gamma-amino acids or peptidemimetics showed drastically decreased activity. On the other hand, the derivatives with alpha-L-amino acids were found to maintain the activity. Among the derivatives prepared in this work, the allylglycine derivative 2s showed the most potent anti-H. pylori activity, with an MIC value of less than 0.006 mug/ml against H. pylori NCTC11637, which is 60-fold greater than the activity of the lead compound pyloricidin C.