We have previously shown that emodin suppresses tyrosine kinase activity of HER-2/neu-encoded p185 neu receptor tyrosine kinase. In this study, we examine the relationship between the chemical structure and the activity of emodin and nine derivatives, and identi®ed that one methyl, one hydroxy, and one carbonyl functional groups are critical for the biological activities of emodin. We also found that one of the derivatives 10-(4-acetamidobenzylidene)-9-anthrone (DK-V-47) is more eective than emodin in repressing the tyrosine phosphorylation of p185 neu and in inhibiting the proliferation and transformation of HER-2/neu-overexpressing human breast cancer cells. Using mutation-activated HER-2/neu transformed 3T3 cells, we also investigated whether emodin and DK-V-47 can inhibit malignant transformation induced solely by the HER-2/neu oncogene. We found that DK-V-47 is more potent than emodin in suppressing transformation phenotypes of activated HER-2/neu transformed 3T3 cells including anchoragedependent and -independent growth, metastasis-associated properties. These results clearly indicate that the inhibition of p185 neu tyrosine kinase by both emodin and DK-V-47 is capable of suppressing the HER-2/neu associated transformed phenotypes including the ability to induce metastatic potential. Our results also support the chemotherapeutic implications of the use of either emodin or DK-V-47 to target HER-2/neu-overexpressing cancer cells.

The biosynthesis of ansatrienin (mycotrienin) has been studied in radioactive and stable isotope feeding experiments with Streptomyces collinus Tü 1892. The m-C7N unit of the ansa ring is efficiently and specifically derived from 3-amino-5-hydroxybenzoic acid; shikimic acid is not incorporated into this part of the molecule but does label the cyclohexanecarboyxlic acid moiety, providing all seven of its carbon atoms. Incorporation of methionine confirms origin of the methoxy group by transmethylation. The D-alanine moiety is derived directly from D-alanine rather than L-alanine. The terminal steps in the conversion of shikimic acid into cyclohexanecarboyxlic acid seem to be sequential reduction of 2,5-dihydrobenzoic acid and cyclohexene-1-carboxylic acid as evidenced by feeding experiments and the detection of a new ansatrienin containing a 1-cyclohexene instead of the cyclohexane moiety.

Using brine shrimp lethality for activity-directed fractionation, goniothalamicin (I), a new tetrahydroxy-mono-tetrahydrofuran fatty acid gamma-lactone (acetogenin), has been isolated from ethanolic extracts of the stem bark of Goniothalamus giganteus Hook. f., Thomas (Annonaceae). This novel compound was found to be cytotoxic and insecticidal and inhibited the formation of crown gall tumors on potato discs. Annonacin (II), the only other reported mono-tetrahydrofuran acetogenin, was also isolated; the previously reported 9ASK (astrocytoma reversal) activity of II was confirmed, and II is now also found to be weakly active against 3PS murine leukemia.

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sulfide, diphenyl disulfide, and diphenyl diselenide, respectively, as well as reduction products 6 and 11. Diphenyl telluride is oxidized to diphenyl telluroxide with 7, but diphenyl selenide is unreactive toward 7. The pertellurane dibromides and dichlorides do not react with olefins in CH2C12 after 48 h in the dark at ambient temperature, although irradiation leads to small amounts of allylic halides. Compounds 9 and 10 are reduced with hydrazine to give ll18 and 1219 in 71% and 89% yields, Br Cl M 12 respectively. All of the pertelluranes were susceptible to