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Antitumor activity of novel ailanthone derivatives in vitro and in vivo

Kato, T.; Suzumura, Y.; Fukushima, M.; Honda, T.; Nakanishi, T.; Noguchi, T.

Anticancer Research 8(4): 573-579

1988

ISSN/ISBN: 0250-7005
PMID: 3178149
Document Number: 310388
The antitumor activities of two ailanthone derivatives with 15.beta.-acyloxy side chains were investigated. The cytotoxic activity of 11.beta., 20-epoxy-1.beta., 11.alpha., 12.alpha.-trihydroxy-15.beta.-((E)-3-methyl-2-octenoyl) oxypicras-3,13(21)-diene-2,16-dione (SUN2071) and 11.beta., 20-epoxy-1.beta., 11.alpha., 12.alpha.-trihydroxy-15.beta.-((E)-2-undecenoyl) oxypicras-3,13(21)-diene-2,16-dione (SUN0237) was close to that of bruceantin and vincristine. SUN2071 was shown to be a potent inhibitor of protein synthesis in L1210 cultured cells. When administered i.p. to i.p. inoculated P388 leukemia mice, daily treatment with SUN2071 and SUN0237 significantly increased the lifespan (increases in lifespan in excess of 100% were achieved). These increases were comparable to those achieved with vincristine. The therapeutic ratio of SUN2071 was also close to that of vincristine. However, the compounds were ineffective when administered as a single injection. Daily i.p. treatment wtih SUN2071 demonstrated significant tumor growth inhibition in mice inoculated s.c. with colon-38 and moderate activity against i.p. L1210 leukemia and i.p. B16 melanoma. The compounds were ineffective when tested against the Lewis lung carcinoma and colon-26. In a preliminary toxicological study, SUN2071 at a therapeutic dose in daily consecutive i.p. injection produced leucopenia.

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