title: Muraymycins, novel peptidoglycan biosynthesis inhibitors: semisynthesis and SAR of their derivatives.
abstract: Sixteen muraymycin derivatives 2-17 were synthesized based on selective reactions of the primary and secondary amino groups of muraymycin C1 (1) with isocyanates and aldehydes. Disubstituted derivatives 3-9 demonstrated no activity against either MraY or MurG at <or=100 microg/mL whereas mono substituted derivatives 11-17 demonstrated good inhibitory activity, well correlated with the lipophilicity of the substituent introduced. In particular, the activity of derivatives 13 and 14 was comparable to that of muraymycin C1 in this assay.
authors.affiliation: Chemical Sciences and Infectious Diseases, Wyeth Research, Pearl River, NY 10965, USA. linf@wyeth.com
authors.forename: Yang-I
authors.initials: YI
authors.lastname: Lin
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.forename: Gerardo D
authors.initials: GD
authors.lastname: Francisco
authors.forename: Leonard A
authors.initials: LA
authors.lastname: McDonald
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Davis
authors.forename: Guy
authors.initials: G
authors.lastname: Singh
authors.forename: Youjun
authors.initials: Y
authors.lastname: Yang
authors.forename: Tarek S
authors.initials: TS
authors.lastname: Mansour
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D002473:Cell Wall / Q000201:enzymology; D057927:Hydrophobic and Hydrophilic Interactions; D009711:Nucleotides; D010455:Peptides; D010457:Peptidoglycan / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000187:drug effects* / Q000494:pharmacology; D013212:Staphylococcus epidermidis / Q000201:enzymology / Q000648:ultrastructure; D013329:Structure-Activity Relationship; D014166:Transferases / Q000037:antagonists & inhibitors*; D017855:Transferases (Other Substituted Phosphate Groups); D014508:Urea
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D009711:Nucleotides; D010455:Peptides; D010457:Peptidoglycan; C475706:muraymycin A1; C475707:muraymycin A3; C475708:muraymycin C1; D014508:Urea; D014166:Transferases; D017855:Transferases (Other Substituted Phosphate Groups); C079803:mraY protein, Bacteria