Antineoplastic Agents, 256. Cell Growth Inhibitory Isocarbostyrils from Hymenocallis

Abstract

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 cytotoxicity 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 tumor 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 or more sensitive than the less sensitive lines.

Pancratistatin Selectively Targets Cancer Cell Mitochondria and Reduces Growth of Human Colon Tumor Xenografts

“…The structurally minimum pharmacophore required for potent anticancer activity has been defined in the pancratistatin series of alkaloids based on a number of structure-activity correlations that have been conducted with both natural and synthetic analogues (37,38). The pharmacophore consists of the 2,3,4-triol structural element in ring-C.…”

“…The pharmacophore consists of the 2,3,4-triol structural element in ring-C. Although not requirements, the pharmacophoric element is moderated slightly by the incorporation of the C7 phenolic hydroxyl group and, interestingly, through the inclusion of a b-benzyloxy substituent on the C1 position (37,39). Because these features are not crucial, they highlight areas where further elaboration is possible on top of the intact pharmacophore.…”

“…To detect generation of ROS, cells were treated with pancratistatin for the indicated time, trypsinized, and incubated with H 2 DCFDA (1 mmol/L) for 45 minutes at 37 C in an opaque 96-well plate. Fluorescence was measured at Ex.…”

In Vitro Activities of Two Antimitotic Compounds, Pancratistatin and 7-Deoxynarciclasine, against Encephalitozoon intestinalis , a Microsporidium Causing Infections in Humans

“…2). Pancratistatin and 7-deoxynarciclasin have been originally identified as antitumor agents extracted from P. littorale, a Hawaiian member of the family Amaryllidaceae, and related species (17,18,19). As many pancratistatin derivatives have been synthesized, we are now testing this family of compounds, with the purpose of identifying a pancratistatin analogue with improved selectivity for microsporidia.…”

Anti-candida activity by <i>Hymenocallis littoralis</i> extracts for opportunistic oral and genital infection <i>Candida albicans</i>

“…The primarily isolated lycorine alkaloid from H. littoralis was proven to have antineoplastic, cytotoxicity and antiviral properties (Ioset et al, 2001;Yew et al, 2010). Pancratistatin from H. littoralis has been proven to be effective against 60 human cancer cell lines including melanoma, brain, colon, lung and renal cancers by U.S. National Cancer Institute's panel (Backhaus et al, 1992;Pettit et al, 1993;Yew et al, 2010). The littoraline alkaloid was demonstrated to have inhibitory activity on HIV reverse transcriptase (Lin et al, 1995).…”