Isolation, purification, and cytotoxicity of 5-methoxypodophyllotoxin, a lignan from a root culture of Linum flavum.
A method has been developed for the large scale isolation of 5-methoxypodophyllotoxin [1] from a high-producing root culture derived from Linum flavum. A closely related lignan, 5'-demethoxy-5-methoxypodophyllotoxin [2], was also present in the root culture and was the cause of the main isolation difficulties. Essential steps in the isolation procedure are CH2Cl2 and XAD-4 extraction and XAD-8 cc followed by Si gel chromatography, using two different mobile phases. The isolated 5-methoxypodophyllotoxin [1] was very pure (greater than 99%) and possessed the desired stereochemical configuration, namely (-)-5-methoxypodophyllotoxin [1]. The in vitro cytotoxicity of 5-methoxypodophyllotoxin [1] against EAT and HeLa cells was determined and compared with those of podophyllotoxin [3], etoposide (VP-16-213) [4], teniposide (VM-26) [5], and 5-methoxypodophyllotoxin-4-beta-D-glucoside [6]. It appeared that 5-methoxypodophyllotoxin [1] has about the same cytotoxic potency as podophyllotoxin [3].
Van Uden
W
W
Laboratory for Pharmacognosy, University of Groningen, The Netherlands.
Homan
B
B
Woerdenbag
H J
HJ
Pras
N
N
Malingré
T M
TM
Wichers
H J
HJ
Harkes
M
M
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D010944:Plants / Q000737:chemistry; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; C074971:5-methoxypodophyllotoxin; D011034:Podophyllotoxin