Synthesis and antitumor activity of novel dolastatin 10 analogs.
Dolastatin 10 (1) is a potent antineoplastic pentapeptide. Novel dolastatin 10 analogs each modified at one of the constituent amino acid derivatives, were synthesized and their antitumor activity was evaluated against P388 leukemia in mice. The structural requirements for antitumor activity are discussed. Some of the analogs, 31c, 35c, 38b, and 50c showed excellent activity in vivo. Highly active 50c, which lacks the thiazole group of 1, was selected for further development as an antitumor agent.
Research Department, Teikoku Hormone Mfg. Co., Ltd., Kawasaki, Japan.
K
K
Miyazaki
M
M
Kobayashi
T
T
Natsume
M
M
Gondo
T
T
Mikami
K
K
Sakakibara
S
S
Tsukagoshi
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D047630:Depsipeptides; D007941:Leukemia P388 / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D047630:Depsipeptides; D009842:Oligopeptides; C064570:dolastatin 10