title: In-vitro antiproliferative activities and kinase inhibitory potencies of meridianin derivatives.
abstract: Marine alkaloid meridianin G derivatives, substituted on the pyrimidine ring by aryl groups, were evaluated for their kinase inhibitory potencies and their in-vitro antiproliferative activities. The derivatives were tested toward a panel of nine protein kinases (KDR, IGF-1R, c-Met, RET, c-Src, c-Abl, PKA, CDK2/cyclin A, and HER-1) and their in-vitro antiproliferative activities were evaluated toward a human fibroblast primary culture and two human solid cancer cell lines (MCF-7 and PA 1). Despite weak kinase inhibitory potencies, high in-vitro antiproliferative activities were found for compounds 5, 7, 12, and 14, which do not interfere with the PA 1 cell cycle and may be considered as direct cytolysis or apoptosis inducers.
authors.affiliation: Laboratoire SEESIB, CNRS UMR 6504, Université Blaise Pascal, Aubière, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Rossignol
authors.forename: Eric
authors.initials: E
authors.lastname: Debiton
authors.forename: Doriano
authors.initials: D
authors.lastname: Fabbro
authors.forename: Pascale
authors.initials: P
authors.lastname: Moreau
authors.forename: Michelle
authors.initials: M
authors.lastname: Prudhomme
authors.forename: Fabrice
authors.initials: F
authors.lastname: Anizon
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005434:Flow Cytometry; D005470:Fluorometry; D006801:Humans; D007202:Indicators and Reagents; D026121:Indole Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D010078:Oxazines; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D014966:Xanthenes
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D026121:Indole Alkaloids; D010078:Oxazines; D014966:Xanthenes; C522699:meridianin G; C005843:resazurin; D010770:Phosphotransferases; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D011493:Protein Kinase C