New potently bioactive alkaloids from Crinum erubescens.
Antimalarial bioassay-guided fractionation of the swamp lily Crinum erubescens led to the isolation of four compounds with potent antiplasmodial activity. Compounds 1 and 2 were determined from their spectroscopic data to be the known pesticidal compound cripowellin A and the known pesticidal and antiproliferative compound cripowellin B. 1D and 2D-NMR techniques were used to determine the identities of 3 and 4 as the new compounds cripowellin C and D. A fifth compound was identified as the known alkaloid hippadine, which was inactive against Plasmodium falciparum. The antiplasmodial IC50values of compounds 1-4 were determined to be 30±2, 180±20, 26±2, and 260±20nM, respectively, and their antiproliferative IC50values against the A2780 human ovarian cancer cell line were 11.1±0.4, 16.4±0.1, 25±2, and 28±1nM.
Department of Chemistry and Virginia Tech Center for Drug Discovery, M/C 0212, Virginia Tech, Blacksburg, VA 24061, United States.
Christopher C
CC
Presley
Department of Biochemistry and Virginia Tech Center for Drug Discovery, M/C 0308, Virginia Tech, Blacksburg, VA 24061, United States.
Priscilla
P
Krai
Department of Biochemistry and Virginia Tech Center for Drug Discovery, M/C 0308, Virginia Tech, Blacksburg, VA 24061, United States.
Seema
S
Dalal
Department of Chemistry and Virginia Tech Center for Drug Discovery, M/C 0212, Virginia Tech, Blacksburg, VA 24061, United States.
Qingxi
Q
Su
Department of Biochemistry and Virginia Tech Center for Drug Discovery, M/C 0308, Virginia Tech, Blacksburg, VA 24061, United States.
Maria
M
Cassera
Natural Products Discovery Institute, 2805 Old Easton Road, Doylestown, PA 18902, United States.
Michael
M
Goetz
Department of Chemistry and Virginia Tech Center for Drug Discovery, M/C 0212, Virginia Tech, Blacksburg, VA 24061, United States. Electronic address: dkingston@vt.edu.
David G I
DGI
Kingston
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D031407:Crinum / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000470:Alkaloids; D000962:Antimalarials
Amaryllidaceae; Antimalarial; Crinum; Cripowellin; Hippadine