Pettit G R, Srirangam J K, Barkoczy J, Williams M D, Boyd M R, Hamel E, Pettit R K, Hogan F, Bai R, Chapuis J C, McAllister S C, Schmidt J M
Department of Chemistry, Arizona State University, Tempe, AZ 85287-2404, USA.
Anticancer Drug Des. 1998 Jun;13(4):243-77.
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.
从印度洋海兔耳状芋螺中提取的具有显著抗癌作用的多拉司他汀10（1a）目前正在进行I期临床试验。已合成了这种特殊肽的38种新的结构修饰物，并针对多种人类和鼠类癌细胞系进行了评估，同时还评估了它们抑制微管蛋白聚合以及长春碱和GTP与微管蛋白结合的能力。发现多拉司他汀10及其一种结构修饰物具有抗真菌活性，而母体化合物的另一种结构修饰物具有抗菌活性。一些新肽接近多拉司他汀10的抗肿瘤效力，尤其是那些用甲硫氨酸、苯丙氨酸或适当取代的苯乙酰胺取代多伊单元的肽。
