Antineoplastic Agents. 592. Highly Effective Cancer Cell Growth Inhibitory Structural Modifications of Dolastatin 10

The dolastatin series of unique peptides, originally discovered as constituents of the sea hare Dolabella auricularia, is of increasing importance in providing biological leads, especially to new and useful anticancer drugs. Dolastatin 10 and three analogues, minor structural modifications designated auristatins, are currently in human cancer clinical trials. The present study was undertaken to explore delivery to the cancer sites by way of phosphate or quinoline modifications. The initial objectives, auristatin TP as sodium phosphate 3b (GI(50) 10(-2)-10(-4) mu g/mL), auristatin 2-AQ (4, GI(50) 10(-2)-10(-3) mu g/mL), and auristatin 6-AQ(5, GI(50) 10(-4) mu g/mL), exhibited superior cancer cell growth inhibitory properties.