meridianin-g and Breast-Neoplasms

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.

Topics: Adenocarcinoma; Antineoplastic Agents; Breast Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cells, Cultured; Enzyme Inhibitors; Female; Fibroblasts; Flow Cytometry; Fluorometry; Humans; Indicators and Reagents; Indole Alkaloids; Oxazines; Phosphotransferases; Protein Kinase C; Protein-Tyrosine Kinases; Receptor Protein-Tyrosine Kinases; Xanthenes