title: Analogues of SB-203207 as inhibitors of tRNA synthetases.
abstract: SB-203207 and 10 analogues have been prepared, by elaboration of altemicidin, and evaluated as inhibitors of isoleucyl, leucyl and valyl tRNA synthetases (IRS, LRS, and VRS, respectively). Substituting the isoleucine residue of SB-203207 with leucine and valine increased the potency of inhibition of LRS and VRS, respectively. The leucine derivative showed low level antibacterial activity, while several of the compounds inhibited IRS from Staphylococcus aureus WCUH29 more strongly than rat liver IRS.
authors.affiliation: Research School of Chemistry, Australian National University, Canberra, ACT. easton@rsc.anu.edu.au
authors.forename: M G
authors.initials: MG
authors.lastname: Banwell
authors.forename: C F
authors.initials: CF
authors.lastname: Crasto
authors.forename: C J
authors.initials: CJ
authors.lastname: Easton
authors.forename: A K
authors.initials: AK
authors.lastname: Forrest
authors.forename: T
authors.initials: T
authors.lastname: Karoli
authors.forename: D R
authors.initials: DR
authors.lastname: March
authors.forename: L
authors.initials: L
authors.lastname: Mensah
authors.forename: M R
authors.initials: MR
authors.lastname: Nairn
authors.forename: P J
authors.initials: PJ
authors.lastname: O'Hanlon
authors.forename: M D
authors.initials: MD
authors.lastname: Oldham
authors.forename: W
authors.initials: W
authors.lastname: Yue
mesh_terms: D000470:Alkaloids / Q000737:chemistry; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007192:Indenes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D007533:Isoleucine-tRNA Ligase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D011725:Pyridines; D051381:Rats; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013457:Sulfur Compounds; D014637:Valine-tRNA Ligase / Q000037:antagonists & inhibitors*
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D007192:Indenes; D011725:Pyridines; C410786:SB 203207; D013449:Sulfonamides; D013457:Sulfur Compounds; C061865:altemicidin; D007533:Isoleucine-tRNA Ligase; D014637:Valine-tRNA Ligase