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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / drug therapy
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Adenocarcinoma / pathology
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Breast Neoplasms / drug therapy
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Breast Neoplasms / pathology
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Cell Cycle / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects*
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Cells, Cultured
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Female
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Fibroblasts / drug effects
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Flow Cytometry
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Fluorometry
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Humans
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Indicators and Reagents
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Indole Alkaloids / chemistry
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Indole Alkaloids / pharmacology*
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Oxazines
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Phosphotransferases / antagonists & inhibitors*
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Protein Kinase C / antagonists & inhibitors
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
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Xanthenes
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Indicators and Reagents
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Indole Alkaloids
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Oxazines
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Xanthenes
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meridianin G
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resazurin
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Phosphotransferases
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Protein-Tyrosine Kinases
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Receptor Protein-Tyrosine Kinases
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Protein Kinase C