The synthesis of etoposide from
simple building blocks requires a costly multistep process, so many attempts
have been made to develop alternative natural sources of podophyllotoxin.
Working with scientists at the University of Mississippi-Oxford, Canel and
Dayan discovered and developed a new method of extracting podophyllotoxin. With
the new procedure the scientists have shown that leaves of an American weed,
P. peltatum, commonly known as mayapple, can yield more podophyllotoxin
than any other source.
"This native North American plant provides a readily available,
plentiful, and renewable source of the drug," says Canel. "Given the
acute toxicity of podophyllotoxin, we think that both the mayapple and the
Indian species produce the compound as a form of protection from insects and
The ARS-Mississippi team has found an efficient way to extract
podophyllotoxins, which the mayapple stores in the form of glucosides. Canel
says the mayapple adds a glucose molecule to podophyllotoxins so the compound
can be safely stored until the plant is attacked.
The key to extraction is to make the plant think it's under attack. By
simulating an herbivore attack, Canel managed to turn on the plant's
glucose-removing machinery. "This allowed the release of large amounts of
stored podophyllotoxins," says Canel.
"The new extraction method is fast, efficient, and inexpensive,"
he says. "And mayapple leaves provide a dependable long-term supply of
podophyllotoxins." If the method is adopted, increased demand for the
American mayapple may make it a new alternative crop, Canel says.
The team has filed a joint patent on the new technology. Talks are in
progress with pharmaceutical firms to license the technology to make this drug
more widely available.By Hank
Becker, Agricultural Research Service Information Staff.
This research is part of New Uses, Quality, and Marketability of Plant
and Animal Products, an ARS National Program (#306) described on the World Wide
Web at http://www.nps.ars.usda.gov/programs/cppvs.htm.
Camilo Canel is in the USDA-ARS
Products Utilization Research Unit, Room 2021, University of Mississippi,
Oxford, MS 38677-8048; phone (662) 915-7965, fax (662) 915-1035.