Chemistry Teams Spend Summer On Anti-Cancer Research

SOCORRO, N.M. August 4, 2009 – Two teams of chemistry professors and students are spending the summer hard at work looking for novel new anti-cancer agents.

Chemistry professor Dr. Ingo Janser, along with three Tech graduate students and two visiting undergraduate students, is synthesizing derivatives of a natural product in an effort to find an effective, well-tolerated anti-cancer agent.

Cynthia Tilley, an undergraduate chemistry major from UT-El Paso, works in Dr. Ingo Janser's lab at New Mexico Tech. She is among a handful of students working on anti-cancer research through the REU program.  Photo by Thomas Guengerich

Chemistry professor Dr. Wim Steelant is overseeing two visiting undergraduate students who are testing the effects of a native Southwest plant on cancer cells.

Steelant’s project focuses on extracting chemical compounds from yerba mansa, a diaphoretic and immune-activating herb used in traditional North American medicine for colds, flu, infections and digestive problems.

Janser’s research focuses on ethacrynic acid, a naturally occurring compound that is used to treat high blood pressure and swelling caused by diseases like congestive heart failure, liver failure and kidney failure. Janser’s research aims to find a derivative of ethacrynic acid that is highly active as an anti-cancer agent and well tolerated by patients at the same time.

Both summer projects are part of ongoing research that each professor is conducting. For the summer, both professors are participating in the Research Experience for Undergraduate program, or REU, which is a National Science Foundation funded project. New Mexico Tech is one of several hundred host institutions for REU summer programs.

The two chemistry projects are among seven REU projects ongoing at New Mexico Tech through August 1.

Janser is mentoring Elizabeth Vogel, a chemistry student at New Mexico Tech, and Cynthia Tilley, a chemistry student at the University of Texas-El Paso.

Janser’s teaching project is equally focused on teaching chemistry lab processes and techniques and on making headway in the search for more active, less toxic cancer drugs.

“This is a learning technique,” he said. “The students are dealing with various chemicals in different reactions. They are learning a variety of different lab techniques like extraction, distillation and flash column chromatography. Hopefully we’ll get a drug that can help patients with cancer.”

Vogel and Tilley are mastering a three-step synthesis process. Tilley, who aims to go to graduate school after finishing at UTEP, said she had limited lab experience before coming to the REU at Tech.

Seth Ferrey and Katie Kaminsky test a series of natural compounds as anti-cancer drugs in Dr. Wim Steelunt's lab at New Mexico Tech. Tilley is from University of Minnesota-Morris. Kaminsky is from Asbury College.  Photo by Thomas Guengerich

“This is more in depth than anything I’ve done,” Vogel said. “I’ll never forget how to do this.”

Step 1 is a nucleophilic substitution reaction, meaning the students are replacing one group of the starting material with another group.

In this step, students are learning to use a reflux condenser and to monitor a reaction by thin layer chromatography, or TLC. Although the basic process is covered in most introductory Organic Chemistry classes, Vogel and Tilley each said they learned the theory, but are now getting very familiar with the laboratory process.

Step 2 is a so-called Friedel-Crafts Acylation, which again involves using a reflux condenser and monitoring the reaction by TLC. The students learn how to deal with moisture and air-sensitive compounds.

Step 3 is an aldol condensation, where the students learn to deal with toxic compounds. In this reaction, the compound is added very slowly to a formaldehyde solution and the solution is stirred vigorously. If done correctly, the product will be an unsaturated carbonyl compound, which is supposed to be the active part of the molecule.

The main goal of Janser’s research is to synthesize a large library of several derivatives of ethacrynic acid. Once the team synthesizes a number of compounds, they will test their effectiveness on human cancer cells in Steelant’s lab. By testing these compounds, he hopes to find highly active anti-cancer agents that have low toxicity.

Steelant has been working for four years on extracting chemical compounds from native Southwest plants.

Biochemistry students Seth Ferrey of the University of Minnesota-Morris and Catherine Kaminski of Asbury College in Kentucky are working on a multi-step process to find the compounds of yerba mansa that are active against cancer.

The plant is divided into four parts – roots, stems, leaves and flowers. They then made extracts from the four parts in three different solutions – water, ethanol and ethyl acetate. Each of the solutions draws out different compounds from the plant – making 12 different extracts/conditions. Each solution is then filtered, and made into a powder, by freeze-drying.

Each of the 12 extracts is then tested for medicinal effectiveness against three types of human cancer cells – for 36 different combinations.

“It’s pretty laborious, but it’s what needs to be done for this project,” Steelant said.

Ferrey and Kaminski have spent long hours in the lab since starting their project. While some of their tasks have been repetitive, their project is far from simple.

They started by determining/testing the toxicity of each of these extracts on the different cancer cell.

“We’re basically determining what extracts are toxic and at what concentration,” Ferrey said. “When we know these values we can continue with other experiments, like growth assays. It’s a big process and we’re just scratching the surface.”

Ferrey and Kaminski conducted experiments to assess the effect of these extracts on cancer cell growth and even went further in determining how this may have been established.

– NMT –

By Thomas Guengerich