naamidine-a and Carcinoma--Squamous-Cell

The known 2-aminoimidazole alkaloid naamidine A (1) was isolated from a Fijian Leucetta sp. sponge as an inhibitor of the epidermal growth factor (EGF) receptor. The compound exhibited potent ability to inhibit the EGF signaling pathway and is more specific for the EGF-mediated mitogenic response than for the insulin-mediated mitogenic response. Evaluation in an A431 xenograft tumor model in athymic mice indicated that naamidine A exhibited at least 85% growth inhibition at the maximal tolerated dose of 25 mg/kg. Preliminary mechanism of action studies indicate that the alkaloid fails to inhibit the binding of EGF to the receptor and has no effect on the catalytic activity of purified c-src tyrosine kinase.

Topics: 3T3 Cells; Alkaloids; Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Cell Division; CSK Tyrosine-Protein Kinase; Enzyme Inhibitors; Epidermal Growth Factor; ErbB Receptors; Imidazoles; Mice; Mice, Nude; Neoplasm Transplantation; Porifera; Protein-Tyrosine Kinases; src-Family Kinases; Transplantation, Heterologous