Abstract |
Eight skin irritant 3-esters with the homologous even number aliphatic acids (acetic to hexadecanoic acid) of the polyfunctional diterpene alcohol ingenol as well as the non- irritant 3-tetradecanoate of delta 7,8-isoingenol were tested for their initiation or ( tumor)-promoting activity in the standardized semi-quantitative initiation/promotion assay on the back skin of NMRI mice. In a corresponding protocol over 48 weeks without preceding initiation, i.e. as a tumorigen, the 3-hexadecanoate of ingenol (3-HI) proved to be practically inactive as compared to the strong response elicited as promoter. Dose/response relations were shown to be positive for both 3-HI and 3-O-tetradecanoylingenol (3-TI), as representative ingenol-3-esters. In assays for structure/activity relations of promoting activity, it turned out that the group of 3-acetate, 3-butyrate and 3-hexanoate of ingenol are very weak to weak promoters. The group of 3-octanoate to 3-HI proved to be strong promoters. Maximal activity was exhibited by 3-TI and it is proposed that this be considered the prototype of the 3-esters of the ingenane type. In semi-quantitative terms it is slightly less active as a skin tumor promoter than the tigliane type 12-O-tetradecanoylphorbol-13-acetate. At the same dose level as 3-TI, the 3-tetradecanoate of delta 7,8-isoingenol was inactive as a promoter.
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Authors | B Sorg, R Schmidt, E Hecker |
Journal | Carcinogenesis
(Carcinogenesis)
Vol. 8
Issue 1
Pg. 1-4
(Jan 1987)
ISSN: 0143-3334 [Print] England |
PMID | 3100081
(Publication Type: Journal Article)
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Chemical References |
- Diterpenes
- Acetone
- 9,10-Dimethyl-1,2-benzanthracene
- ingenol
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Topics |
- 9,10-Dimethyl-1,2-benzanthracene
- Acetone
- Animals
- Diterpenes
(toxicity)
- Dose-Response Relationship, Drug
- Female
- Isomerism
- Mice
- Skin
(drug effects)
- Skin Neoplasms
(chemically induced)
- Structure-Activity Relationship
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