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

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.

• Authors: M Hirota, M Suganuma, S Yoshizawa, T Horiuchi, M Nakayasu, M Hasegawa, Y Endo, K Shudo, H Fujiki
• Journal: Japanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 78 Issue 6 Pg. 577-82 (Jun 1987) ISSN: 0910-5050 [Print] Japan
• PMID: 3112073 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Indoles
• Lactams
• Lyngbya Toxins
• teleocidins
• indolactam V
• Protein Kinase C
• Ornithine Decarboxylase
• Tetradecanoylphorbol Acetate

Topics

• Animals
• Cell Adhesion (drug effects)
• Cell Line
• Dose-Response Relationship, Drug
• Enzyme Induction
• Humans
• Indoles
• Lactams
• Leukemia, Myeloid, Acute (pathology)
• Lyngbya Toxins
• Mice
• Neoplasms, Experimental (chemically induced)
• Ornithine Decarboxylase (biosynthesis)
• Protein Kinase C (metabolism)
• Skin (enzymology)
• Structure-Activity Relationship
• Tetradecanoylphorbol Acetate (metabolism)