The bulbs of Pancratium littorale collected in Hawaii were found to contain a new phenanthridone biosynthetic product designated pancratistatin (4a) that proved to be effective (38-106% life extension at 0.75-12.5 mg/kg dose levels) against the murine P-388 lymphocytic leukemia. Pancratistatin also markedly inhibited (ED50, 0.01 microgram/ml) growth of the P-388 in vitro cell line and in vivo murine M-5076 ovary sarcoma (53-84% life extension at 0.38-3.0 mg/kg). An X-ray crystal structure determination of pancratistatin monomethyl ether (4c) and a detailed high resolution (400 MHz) nmr study of pancratistatin and its pentaacetate (4b) completed assignment of structure 4a. Companion antineoplastic constituents of P. littorale were found to be narciclasine (2c) and its 7-deoxy derivative (2a). The structure of 7-deoxynarciclasine (2c) was also confirmed by an X-ray crystallographic analysis.
fancratium iittorale Jacq. collected in Hawaii has been found to produce a new phenanthridone, pancratistatin, that significantly inhibits growth of the murine P388 lymphocytic leukaemia; an X-ray crystal structure determination of pancratistatin monomethyl ether (Ic) was employed to assign structure ( l a ) to pancratistatin.Because of early2 interest in certain medicinal and/or poisonous plant species of the relatively large Amaryllidaceae family? about 10% have been investigated for alkaloid constituents, and over 70 such basic metabolites have been isolated.4 Some 30 Amaryllidaceae species have found use in primitive treatment of cancer.' Most significantly, in the U.S. National Cancer Institute's (N. C. I .) exploratory plant evaluation programme some Amaryllidaceae species have yielded extracts with confirmed levels of anticancer activity. We now report that roots of the Hawaiian Parzcratiurn liftorale Jacq.t contain a new anticancer (3$--106% life extension at 0.75-12.5 mg dose levels using the murine P388 lymphocytic leukaemia, PS system, and 53-84% life extension at 0.38-3.0 mgikg against the murine M5076 ovary sarcoma) biosynthetic product herein named pancratistatin (la).The bulb section (45 kg) of P. littorale was extracted with methylene chloride-methanol-water and pancratistatin was concentrated (separation was guided primarily by bioassay using the PS in vivo system) in a butyl alcohol extract of the aqueous phase. Purification of half of the crude product employing selective solubility properties and gel permeation chromatography (Sephadex LH-20) afforded 6.5 g (0.028% t The more usual range is tropical Africa to Asia; also known as Hjwwnocallis littoralis (Jacq .) Salisb. OR^ OR 0 yield) of pancratistatin (la) that separated from dimethylformamide-methanol-ether as a colourless solid, m.p. 322-324 "C, electron impact mass spectrum m l z 325 ( M f . C14H15NOX); [cwID'4 + 48" ( c 1.0, Me,SO); A , , ,(log E) 209 (sh), 219 (sh), 233 (4.32), 278 (3.91), and 308 (br. sh) nm; i.r. (
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