Synthetic analogues (indolactams) of (-)-indolactam-V are new congeners of the teleocidin class of tumor promoters

Mitsuru Hirota, Masami Suganuma, Shigeru Yoshizawa, Takahiko Horiuchi, Michie Nakayasu, Masashi Hasegawa, Yasuyuki Endo, Koichi Shudo, Hirota Fujiki

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Abstract

(-)-Indolactam-V, which has the partial structure of teleocidins A and B, and has tumor-promoting activity, is a good model for use in studies on the relation between structure and tumor-promoting activity, whereas (+)-indolactam-V has no tumor-promoting activity. In this work, five racemic indolactams differing only in their alkyl group at C-12 of (-)-indolactam-V were synthesized and tested for biological and biochemical activities related to tumor promotion. The activities tested were inductions of ornithine decarboxylase in mouse skin and human promyelocytic leukemia (HL-60) cell adhesion, inhibition of specific [3H]12-O-tetradecanoyl-phorbol-13-acetate binding to a mouse particulate fraction and activation of protein kinase C in vitro. The results showed that (±)-indolactam-L and (±)-indolactam-F had almost the same activities as (±)-indolactam-V, suggesting that (-)-indolactam-L and (-)-indolactam-F are new tumor promoters with as high potency as (-)-indolactam-V. (±)-Indolactam-t-L, which has a highly lipophilic group at C-12 of (-)-indolactam-V, showed the highest activities in the above tests. (-)-Indolactam-t-L might have stronger tumor-promoting activity than (-)-indolactam-V. Furthermore, the results with (-)-indolactam-t-L indicated the possibility of designing new tumor promoters with stronger activity than teleocidin.

Original languageEnglish
Pages (from-to)577-582
Number of pages6
JournalJapanese Journal of Cancer Research
Volume78
Issue number6
Publication statusPublished - Jun 1 1987
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Hirota, M., Suganuma, M., Yoshizawa, S., Horiuchi, T., Nakayasu, M., Hasegawa, M., Endo, Y., Shudo, K., & Fujiki, H. (1987). Synthetic analogues (indolactams) of (-)-indolactam-V are new congeners of the teleocidin class of tumor promoters. Japanese Journal of Cancer Research, 78(6), 577-582.