title: Synthesis and anti-Helicobacter pylori activity of pyloricidin derivatives I. Structure-activity relationships on the terminal peptidic moiety.
abstract: 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 a-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 microg/ml against H. pylori NCTC11637, which is 60-fold greater than the activity of the lead compound pyloricidin C.
authors.affiliation: Pharmaceutical Research Division, Takeda Chemical Industries, Ltd, Osaka, Japan. Hasuoka_Atsushi@takeda.co.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hasuoka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishikimi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Keiji
authors.initials: K
authors.lastname: Kamiyama
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakao
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Miyagawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Nishimura
authors.forename: Masahiko
authors.initials: M
authors.lastname: Fujino
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D016480:Helicobacter pylori / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010455:Peptides; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; C456045:pyloricidin B; C456046:pyloricidin C