title: Isosteric replacement of the Z-enone with haloethyl ketone and E-enone in a resorcylic acid lactone series and biological evaluation.
abstract: The synthesis of a small library of resorcylic acid lactones and evaluation of their biological properties as kinase inhibitors is described. Within the series E-enones were found more active than corresponding Z-enones as inhibitors of a subset of kinases containing a conserved cysteine. Replacement of the enone moiety with a β-haloketone group led to compounds with an interesting kinase selectivity profile and also antiproliferative activity against Jurkat cells. An E-enone derivative also showed activity against capillary tube formation based on a co-culture of primary human umbilical cord endothelial cells (HUVECs) and vascular smooth muscle cells (vSMCs).
authors.affiliation: School of Chemistry, National University of Ireland, Galway, University Road, Galway, Ireland.
authors.forename: Carmela
authors.initials: C
authors.lastname: Napolitano
authors.forename: Alessandro
authors.initials: A
authors.lastname: Natoni
authors.forename: Corrado
authors.initials: C
authors.lastname: Santocanale
authors.forename: Lasse
authors.initials: L
authors.lastname: Evensen
authors.forename: James B
authors.initials: JB
authors.lastname: Lorens
authors.forename: Paul V
authors.initials: PV
authors.lastname: Murphy
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002478:Cells, Cultured; D006801:Humans; D007536:Isomerism; D007659:Ketones / Q000737:chemistry*; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007659:Ketones; D007783:Lactones; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases