TUMOR INHIBITORS .46. VERNOLEPIN, A NOVEL SESQUITERPENE DILACTONE TUMOR INHIBITOR FROM VERNONIA HYMENOLEPIS A RICH

An alcoholic extract of Vernonia hymenolepis A. Rich, was found to show significant inhibitory activity in vitro against cells derived from human carcinoma of the nasopharynx (KB) carried in tissue culture. The isolation and structural elucidation are reported of vernolepin (1) and vernomenin (5), two novel elemanolide dilactones from V. hymenolepis. Vernolepin showed significant in vitro cytotoxicity (KB) and in vivo tumor inhibitory activity against Walker intramuscular carcinosarcoma in rats. Elemental analysis and mass spectrometry indicated a C15H16O5 molecular formula for vernolepin. Chemical and spectral evidence indicated the presence of two α,β-unsaturated lactone functions, a secondary alcohol, an additional double bond, and, therefore, a monocarbocyclic ring skeleton. The structure and stereochemistry of 1 were established by X-ray crystallographic examination of the p-bromobenzenesulfonate, 3. Vernomenin (5) showed similar chemical properties to vernolepin, and its structure was proven by its conversion to 7, one of the transformation products of vernolepin, and by comparison of the nmr spectra of 2 and 6, the respective acetates of 1 and 5. Certain aspects of the structure of the lactones in relation to the tumor-inhibitory properties are discussed. © 1969, American Chemical Society. All rights reserved.