title: Novel antibiotics for the treatment of gram-positive bacterial infections.
abstract: The natural dipeptide antibiotic TAN 1057 A,B displays excellent antibacterial activity against staphylococci including methicillin resistant Staphylococcus aureus. However, the in vitro activity against additional Gram-positive strains, in particular pneumococci and Enterococcus faecalis, proved to be considerably lower. We report the synthesis and pharmacological evaluation of new derivatives of this natural product that displayed increased antibacterial potency against staphylococci and were also active against pneumococci. In particular, the analogues bearing modified beta-homoarginine side chains with methylated guanidine moieties were shown to be significantly more potent than the natural product TAN 1057 A,B.
authors.affiliation: Business Group Pharma, Research, BAYER AG, Wuppertal D-42096, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Brands
authors.forename: Rainer
authors.initials: R
authors.lastname: Endermann
authors.forename: Reinhold
authors.initials: R
authors.lastname: Gahlmann
authors.forename: Jochen
authors.initials: J
authors.lastname: Krüger
authors.forename: Siegfried
authors.initials: S
authors.lastname: Raddatz
authors.forename: Jürgen
authors.initials: J
authors.lastname: Stoltefuss
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Belov
authors.forename: Shamil
authors.initials: S
authors.lastname: Nizamov
authors.forename: Viktor V
authors.initials: VV
authors.lastname: Sokolov
authors.forename: Armin
authors.initials: A
authors.lastname: de Meijere
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001120:Arginine / Q000737:chemistry; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008826:Microbial Sensitivity Tests; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018805:Sepsis / Q000401:mortality / Q000517:prevention & control; D013210:Staphylococcus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: C465773:5-(N-(3-amino-6-(1-methylguanidin-1-yl)hexanoyl)-N-methylamino)-5,6-dihydro-2-ureidopyrimid-4(1H)-one; D000900:Anti-Bacterial Agents; D004151:Dipeptides; D006146:Guanidines; D011744:Pyrimidinones; C081415:TAN 1057A; C081416:TAN 1057B; D001120:Arginine