Antitumor activity of MST-16, a novel derivative of bis(2,6-dioxopiperazine), in murine tumor models.
We studied the antitumor activity of newly synthesized bis(1-acyloxymethyl) derivatives of 4,4'-(1,2-ethanediyl)bis(2,6-piperazinedione) using i.p.-i.p. models of P388 leukemia and B16 myeloma. As a result, we found 4,4'-(1,2-ethanediyl)bis(1-isobutoxycarbonyloxymethyl-2,6-piperazi nedione) (MST-16) to possess considerable therapeutic activity. MST-16 showed not only marked life-prolonging effects in both P388 leukemia- and B16 melanoma-bearing mice but also a greater therapeutic ratio than did its parent compounds, ICRF-154 and ICRF-159. Further studies revealed that MST-16 has considerable therapeutic activity against a number of other tumors such as ascitic forms of L1210 leukemia, colon 26 adenocarcinoma, and MH-134 hepatoma and solid forms of B16 melanoma, Lewis lung carcinoma, colon 38 adenocarcinoma, and M5076 fibrosarcoma. These results suggest that MST-16 is very promising as an antitumor agent.
Narita
T
T
Research Laboratory, Zenyaku Kogyo Co., Ltd., Tokyo, Japan.
Yaguchi
S
S
Komatsu
T
T
Takase
M
M
Hoshino
A
A
Inaba
M
M
Tsukagoshi
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D007941:Leukemia P388 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D010879:Piperazines / Q000627:therapeutic use*; D011929:Razoxane / Q000031:analogs & derivatives / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D010879:Piperazines; D011929:Razoxane; C000283:1,2-bis(3,5-dioxopiperazin-1-yl)ethane; C057773:sobuzoxane