title: Rhodanine-3-acetic acid derivatives as inhibitors of fungal protein mannosyl transferase 1 (PMT1).
abstract: The first inhibitors of fungal protein: mannosyl transferase 1 (PMT1) are described. They are based upon rhodanine-3-acetic acid and several compounds have been identified, for example, 5-[[3-(1-phenylethoxy)-4-(2-phenylethoxy)phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid (5a), which inhibit Candida albicans PMT1 with IC(50)s in the range 0.2-0.5 microM. Members of the series are effective in inducing changes in morphology of C. albicans in vitro that have previously been associated with loss of the transferase activity. These compounds could serve as useful tools for studying the effects of protein O-mannosylation and its relevance in the search for novel antifungal agents.
authors.affiliation: Department of Medicinal Chemistry, 4-10 The Quadrant, Abingdon Science Park, Abingdon, Oxfordshire OX14 4YS, UK. mike.orchard@celltechgroup.com
authors.forename: Michael G
authors.initials: MG
authors.lastname: Orchard
authors.forename: Judi C
authors.initials: JC
authors.lastname: Neuss
authors.forename: Carl M S
authors.initials: CM
authors.lastname: Galley
authors.forename: Andrew
authors.initials: A
authors.lastname: Carr
authors.forename: David W
authors.initials: DW
authors.lastname: Porter
authors.forename: Phillip
authors.initials: P
authors.lastname: Smith
authors.forename: David I C
authors.initials: DI
authors.lastname: Scopes
authors.forename: David
authors.initials: D
authors.lastname: Haydon
authors.forename: Katherine
authors.initials: K
authors.lastname: Vousden
authors.forename: Colin R
authors.initials: CR
authors.lastname: Stubberfield
authors.forename: Kate
authors.initials: K
authors.lastname: Young
authors.forename: Martin
authors.initials: M
authors.lastname: Page
mesh_terms: D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects / Q000201:enzymology; D008364:Mannosyltransferases / Q000037:antagonists & inhibitors*; D008826:Microbial Sensitivity Tests; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D012236:Rhodanine; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase