Cytotoxic activity of some phenanthroindolizidine N-oxide alkaloids from Cynanchum vincetoxicum.
Two previously known phenanthroindolizidine alkaloids, (-)-10beta-antofine N-oxide (1) and (-)-10beta, 13aalpha-14beta-hydroxyantofine N-oxide (2), and a novel alkaloid, (-)-10beta,13aalpha-secoantofine N-oxide (3), were isolated from aerial parts of Cynanchum vincetoxicum. Their structures were established by means of NMR methods, including COSY, NOESY, HSQC, and HMBC experiments, as well as from their CD spectra. Cytotoxic activity of the alkaloids was assessed in vitro using both a drug-sensitive KB-3-1 and a multi-drug-resistant KB-V1 cancer cell line. The antofine derivatives (1 and 2) showed pronounced cytotoxicity against the drug-sensitive cell line (IC(50) values about 100 nM), whereas the secoantofine derivative (3) was considerably less active. The KB-V1 cell line showed a marginal resistance against all alkaloids, demonstrating that these compounds are poor substrates for the P-glycoprotein (P-170) efflux pump.
Staerk
D
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Department of Medicinal Chemistry, Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Christensen
J
J
Lemmich
E
E
Duus
J O
JO
Olsen
C E
CE
Jaroszewski
J W
JW
D000470:Alkaloids / Q000302:isolation & purification* / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification* / Q000494:pharmacology; D002942:Circular Dichroism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007212:Indolizines; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010616:Phenanthrenes / Q000302:isolation & purification* / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D014407:Tumor Cells, Cultured
C420910:10,13a,14-hydroxyantofine N-oxide; C420908:10,13a-secoantofine N-oxide; C420907:10-antofine N-oxide; D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D007212:Indolizines; D010616:Phenanthrenes