ISOLATION AND STRUCTURE ELUCIDATION OF ANTINEOPLASTIC AGENTS FROM PLANTS; HELICTERES ISORA AND STIZOLOPHUS BALSAMITUS

A cytotoxic sesquiterpene was isolated in 0.23% yield from the dry epigeal portion of Stizolophus balsamitus Cass. ex Takht. (Centaurea balsamita Lam.) (Asteraceae) collected in Iran. Based on IR, UV, mass, CD, and NMR spectral data, the compound was identified as stizolicin which had previously been isolated from the same plant. Stizolicin shows significant cytotoxicity in the PS lymphocytic leukemia cell culture (LD 50 = 0.9 mcg/ml) but only marginal activity in vivo against murine P-388 leukemia. The stereochemistry of stizolicin was corrected to a trans,trans germacranolide on the basis of simultaneous application of lanthanide shift reagents and nuclear Overhauser effects in the NMR. This conclusion was confirmed by conversion of stizolicin to isospiciformin, a compound for which the stereochemistry is known. A chemotaxonomic review of the Composite tribe Cardueae revealed that all sesquiterpene lactones in the taxon appear to be based on trans,trans germacranolides. Fractionation of Helicteres isora L. (Sterculiaceae) root-extracts guided by cytotoxic activity in the KB nasopharyngeal carcinoma resulted in the isolation of two highly cytotoxic compounds (ED(,50) (LESSTHEQ) 10(\u27-5) and = 7.6 x 10(\u27-5) mcg/ml), cucurbitacin B and isocucurbitacin B. The compounds were identified on the basis of UV, IR, mass, and NMR spectral data, and cucurbitacin B was compared with an authentic sample