Tenulin

J Nat Prod. 1987 Jul-Aug;50(4):690-5.

Mode of action of the sesquiterpene lactone, tenulin, from Helenium amarum against herbivorous insects.[Pubmed: 3430166]

Tenulin [1], a sesquiterpene lactone from Helenuim amarum, is a potent antifeedant to the European corn borer Ostrinia nubilalis.
METHODS AND RESULTS:
At 3 mumol/g in artificial diets, 1 reduced growth and delayed larval development of O. nubilalis and the variegated cutworm Peridroma saucia larvae. An especially pronouned carry-over effect in O. nubilis was substantial reduction in fecundity of adult moths resulting from treated larvae. The LD50 (lethal dose for 50% mortality) of 1 by injection in the migratory grasshopper Melanoplus sanguinipes was 0.88 mumol/insect. Toxicity in M. sanguinipes was antagonized by co-administration of cysteine, suggesting that the cyclopentenone group of Tenulin undergoes Michael addition of biological nucleophiles in vivo.
CONCLUSIONS:
This mechanism was partially confirmed by the finding that only Tenulin analogues capable of acting as electrophic acceptors had significant antifeedant activity.

Science. 1977 Apr 29;196(4289):533-6.

Sesquiterpene antitumor agents: inhibitors of cellular metabolism.[Pubmed: 191909]

METHODS AND RESULTS:
Helenalin and Tenulin injected into CF1 male mice bearing Ehrlich ascites tumors inhibit DNA synthesis and DNA polymerase enzymatic activity in the tumor cells. Helenalin inhibited protein synthesis. Both drugs increased the concentration of adenosine 3',5'-monophosphate, and interfered with glycolytic and mitochondrial energy processes. Cholesterol synthesis was also inhibited, resulting in lower serum cholesterol levels in tumor-bearing animals. Data obtained in vitro indicate that the cyclopentenone-bearing sesquiterpene lactone and related compounds do not alkylate puring bases of nucleic acids but rather undergo a Michael-type addition reaction with the sulfhydryl groups of reduced glutathione and l-cysteine.
CONCLUSIONS:
Thus, the inhibition of cellular enzyme activities and metabolism that has been observed with these drugs might be explained by the occurrence of a Michael-type teaction.