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  • Title: Antineoplastic agents 365. Dolastatin 10 SAR probes.
    Author: Pettit GR, Srirangam JK, Barkoczy J, Williams MD, Boyd MR, Hamel E, Pettit RK, Hogan F, Bai R, Chapuis JC, McAllister SC, Schmidt JM.
    Journal: Anticancer Drug Des; 1998 Jun; 13(4):243-77. PubMed ID: 9627667.
    Abstract:
    The remarkable anticancer drug dolastatin 10 (1a) from the Indian Ocean sea hare Dolabella auricularia is currently undergoing phase I clinical trials. Thirty-eight new structural modifications of this unusual peptide have been synthesized and evaluated against a variety of human and murine cancer cell lines, and for their ability to inhibit tubulin polymerization and vinblastine and GTP binding to tubulin. Dolastatin 10 and one structural modification was found to have antifungal activity, while one other structural modification of the parent compound exhibited antibacterial activity. Some of the new peptides approximated the antineoplastic potency of dolastatin 10, especially those based on replacement of the Doe unit with Met, Phe or an appropriately substituted phenylethylamide.
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