title: Synthesis and biological evaluation of monoindolyl and indolocarbazolyl oxazolones and imidazolones.
abstract: Eight compounds structurally related to protein kinase C inhibitor MDL 27032 and substituted with indole moieties were synthesized. Their activities towards protein kinase C (PKC) and protein kinase A (PKA) were determined. Their effect on PKC-mediated contraction of rat tracheal smooth muscle, their antiproliferative activity on two murine tumor cell lines, melanoma B16 and leukemia P388 and their antimicrobial activity on a gram-positive bacterium Bacillus cereus were also examined. The mammalian and bacterial cell antiproliferative activity, as well as vasorelaxant effect, observed for some of them could not be correlated to PKC or PKA inhibition. Only bulky bis-indolyl compounds exhibited biological activity in these experiments. Rigid indolocarbazoles had the strongest antiproliferative activity.
authors.affiliation: Université Blaise Pascal, Synthèse, Electrosynthèse et Etude de Systèmes à Intérĕt Biologique, UMR 6504 du CNRS, Aubière, France.
authors.forename: E R
authors.initials: ER
authors.lastname: Pereira
authors.forename: M
authors.initials: M
authors.lastname: Prudhomme
authors.forename: M
authors.initials: M
authors.lastname: Sancelme
authors.forename: M
authors.initials: M
authors.lastname: Ollier
authors.forename: D
authors.initials: D
authors.lastname: Severe
authors.forename: J F
authors.initials: JF
authors.lastname: Riou
authors.forename: H
authors.initials: H
authors.lastname: Crevel
authors.forename: J P
authors.initials: JP
authors.lastname: Savineau
authors.forename: D
authors.initials: D
authors.lastname: Fabbro
authors.forename: T
authors.initials: T
authors.lastname: Meyer
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D010080:Oxazoles / Q000737:chemistry* / Q000494:pharmacology; D010081:Oxazolone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D010080:Oxazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D014665:Vasodilator Agents; C069455:4-propyl-5-(4-pyridinyl)-2(3H)-oxazolone; D010081:Oxazolone; D011494:Protein Kinases; D011493:Protein Kinase C