Synthesis and Anti-Helicobacter pylori Activity of Pyloricidin Derivatives: II. The Combination of Amino Acid Residues in the Dipeptidic Moiety and its Effect on the Anti-Helicobacter pylori Activity

The novel natural antibiotics pyloricidin A, B and C, consisting of a common (2S, 3R, 4R, 5S)-5-amino-2, 3, 4, 6-tetrahydroxyhexanoyl-β-D-phenylalanine moiety and a terminal peptidic moiety (pyloricidin A: L-valine-L-valine-L-leucine; pyloricidin B: L-valine-L-leucine; pyloricidin C: L-leucine), exhibit potent and highly selective anti-Helicobacter pylori activity. In order to develop more potent compounds and to investigate structure activity relationships for the peptidic moiety with regard to the combination of amino acids, a series of derivatives with various dipeptidic moieties were prepared and evaluated for their anti-H. pylori activity. The combination of the two amino acids in the moiety was found to have a significant effect on the activity; the compound with Nva-Abu showed excellent anti-H pylori activity with an MIC value of 0.013μg/ml against H. pylori TN2. In addition, this compound was found to show 60% clearance of H. pylori from infected Mongolian gerbils upon repetitive oral administration (10mg/kg, b. i. d. for 7 days).