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University’s natural products research on cutting edge

Oxford — Imagine in the future eating a handful of blueberries instead of taking a pill to keep your cholesterol in check. Or, imagine that the newest effective treatment for breast cancer has been developed from lizard’s tail (Saururus cernuus), a common wetlands plant in Mississippi, and that the University of Mississippi has patent rights to the new anti-cancer pharmaceutical.

Both of those potential life-saving natural drugs are currently under study and development at the university’s National Center for Natural Products Research (NCNPR).
Dr. Dale Nagle, associate professor of pharmacognosy at the Ole Miss School of Pharmacy, said laboratory tests show that a group of compounds in lizard’s tail destroy tumor cells.

“These are some of the most potent compounds ever found to inhibit these targets,” Nagle said “It’s exciting because if these compounds work in humans the same way as they do in the lab, we could kill cancer cells without the nasty side-effects of conventional chemotherapy.”

The findings were reported in a recent issue of the Journal of Natural Products.

Nagle and other members of the research team are investigating several promising compounds as part of a four-year, $1-million grant from the National Cancer Institute to discover new drugs from plants and animals that can be used for the treatment of breast cancer. Nagle teamed with Dr. Yu-Dong Zhou, a molecular biologist from the university’s NCNPR, postdoctoral research associates Dr. Chowdhury Faiz Hossain and Dr. Yong-Pil Kim, and Tyler Hodges, a graduate student in pharmacognosy.

“Current chemotherapeutic drugs have saved a lot of people, but failed for many others,” Zhou said. “However, rapid advances in biomedical research during the past two decades now provide scientists with exciting new opportunities to discover drugs that can kill cancer cells while sparing normal cells.”

Dr. Walter Chambliss, director of technology management at the university, said the pharmaceutical industry moved away from natural products drug discovery in the mid-1990s, even though 50% of the drugs on the market can be traced to a compound first identified in nature.

“The center is filling this critical gap in drug discovery by partnering with industrial partners to advance the center’s drugs through preclinical and clinical development,” Chambliss said.

Allyson Best, a market analyst at the National Center for Natural Products Research, said the cancer compounds from lizard’s tail have a chance to follow in the path of other top-selling chemotherapy products developed from natural sources. For example, Taxol, which is used to combat breast and ovarian cancer, is a derivative of the yew tree.
Best said nature affords researchers a diversity of compounds much greater than what can be created solely in a lab.

“Nature provides an unlimited number of unique chemicals that we have only begun to take a look at,” Best said. “Our work includes investigating higher plants and marine organisms such as sponges and algae.”

In addition to studying natural compounds for treating breast cancer, the center is also investigating new anti-malaria drugs. Malaria is still one of the worst disease problems in the world. But because the disease is primarily seen in Third World countries, the market doesn’t support a lot of drug development.

“Malaria is still killing millions of children,” Best said. “It is a phenomenal figure.”

Malaria infects an estimated 300 million to 500 million people around the world, killing more than a million people — mostly children — every year. The malaria work done at Ole Miss is conducted under the Medicines for Malaria Venture supported by a consortium including the world’s largest pharmaceutical companies and The Gates Foundation.

A unique feature of the natural products center, which employs 100 people, is that there is a USDA unit in the same building that has 35 employees working to develop naturally occurring herbicides and pesticides, and potential medicines from crops.

“We work very closely with the USDA unit,” Best said. “At one end of the hall, we can investigate a natural product as a potential drug for human patients suffering from life-threatening fungal diseases. And, at other end of the hall, we can investigate the same compound as an anti-fungal treatment for plants. We feel like we are a very unique organization and there is not another research organization in the country that is able to do this type of work as efficiently we can.”

There is a strong focus on technology transfer through commercialization licensing efforts.

“Our mandate is to improve human health and agricultural productivity through the discovery, development and commercialization of phamaceuticals and agrochemicals derived from natural products,” Best said. “We have a strong commitment to partnering with industry to ensure that we meet that mission and have a beneficial impact on the state and the world.”

The NCNPR and the School of Pharmacy have signed more than 15 license agreements in the past six years, in addition to many more research and development agreements with research organizations.

The work at the USDA Agricultural Research Service (ARS) ranges from development of more environmentally friendly algaecides, pesticides and herbicides to genetically engineering blueberries to contain larger quantities of a compound that helps reduce cholesterol levels.
Dr. Stephen O. Duke, research leader of the ARS group, said a product from blueberries, developed by Dr. Agnes Rimando of ARS and Dr. Dennis Feller of Ole Miss, could result in a lower cost cholesterol drug. Blueberries have a natural substance that lowers cholesterol.

In hamster studies, it works as well as one of the leading medicines for cholesterol reduction. A patent is in process on this natural compound as a pharmaceutical.
With genetic engineering, the USDA hopes to create blueberries that contain more of the substance. Instead of having to take a pill, you could just eat blueberries.

“It is almost a miracle,” Duke said. “This compound is found in blueberries so people are eating it all the time. There has been a lot of publicity about the work that Dr. Rimando has done on this.”

Dr. Kevin Schrader of the ARS group, along with Dr. Dhammika Nanayakkara of the NCNPU, have developed a natural product-derived algaecide that is being patented for use in warm water aquaculture to get rid of the blue green algae that causes flavor problems in catfish.

“We have a couple companies interested in that, Duke said. “They are interested in developing it for use in aquariums and aquaculture. In field tests, it seems to be as or more effective than current products in use. It is potentially more environmentally benign than current products. This would give farmers another alternative. The current products used, diuron and copper compounds, kill all the algae. Some green algae are generally beneficial, so you are disturbing the pond ecology by killing all the algae. What we have is about 1,000 times more effective on the algae we do want to kill.”

Other efforts include developing a natural poison for termites, and natural insect repellents.

“We are also working on making plants produce their own natural herbicides so you can reduce the amount of synthetic herbicide used or maybe even eliminate the herbicide,” Duke said. “That is a long range project.”

For more information about the School of Pharmacy, with links to the Department of Pharmacognosy and the National Center for Natural Products Research, go to the Web site http://www.olemiss.edu/depts/ pharmacy/index.html.

Contact MBJ contributing writer Becky Gillette at bgillette@bellsouth.net.


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