ANTINEOPLASTIC AGENTS .256. CELL-GROWTH INHIBITORY ISOCARBOSTYRILS FROM HYMENOCALLIS

The bulbs of Hymenocallis littoralis, collected in Hawaii and horticulturally grown in Arizona, and bulbs of Hymenocallis caribaea and Hymenocallis latifolia, collected in Singapore, were found to contain a cytotoxic, isocarbostyril-type biosynthetic product, 7-deoxy-trans-dihydronarciclasine [2]. This new compound inhibited the cytopathicity and/or replication of various viruses. Companion cytotoxic constituents of H. littoralis and Hymenocallis sp. were found to be pancratistatin [1), narciclasine [5], and 7-deoxynarciclasine [4). These four compounds, along with four other closely related compounds, were comparatively evaluated in the National Cancer Institute's in vitro cytocoxicity panel. Although there were striking differences in overall potency, some of the compounds shared a highly characteristic differential cytotoxicity profile against the 60 diverse human rumor cell lines comprising the NCI panel. As a group, the melanoma subpanel lines were most sensitive; certain individual lines within other subpanels (eg., NSC lung, colon, brain, renal) were as much as a thousand-fold of more sensitive than the less sensitive lines.