CSUDH professor seeks novel lead compound to develop new drug for treating cancer

Does anyone have a cardiac pacemaker or medical device implants? How about keys, a mobile phone, or even a wallet? We wouldn't want anything to get damaged or erased."

These are questions Patrick Still, assistant professor of chemistry and biochemistry at California State University, Dominguez Hills (CSUDH), gingerly asks people who venture into the new campus Nuclear Magnetic Resonance (NMR) Facility and approach the new JEOL 400 MHz NMR spectrometer, which the Still Lab uses for cancer research.

Still uses the NMR spectrometer to conduct his research on plant extracts he procured from the National Cancer Institute (NCI) Active Repository Program. The extracts were prepared from plants originating in tropical regions throughout the world that show activity in the NCI-60 Human Tumor Cell Lines Screen, a collection of 60 cell lines found in different types of cancers.

"We use biological screening to direct which chemicals in the plant extracts we target for figuring out the structure using NMR methods, an iterative process known as bioassay-guided fractionation. We then test pure compounds against brain cancer cells," said Still, the principle investigator of the project who works within the field of natural products chemistry, research that intersects organic chemistry and analytical chemistry.

The payoff would be finding a novel lead compound that could be developed into a drug for treatment of cancer. That would be the ultimate discovery. – Patrick Still

The 400 MHz NMR is the largest research-infrastructure purchase in CSUDH campus history. Still selected, configured, and coordinated the $400,000 purchase through interaction with campus finance, facilities and other administrators during his first year of teaching at the university. The purchase of the NMR is a critical step for CSUDH in buttressing the research infrastructure of the Department of Chemistry, according to Still, who assumed the role of NMR coordinator in 2015.

The cost was worth it. NMR spectroscopy not only detects and measures components in plant extracts and other complex mixtures, but can also verify purity, identity, and composition. The instrument makes the lab's current project focused on the discovery of natural product inhibitors of a key enzyme in cancer progression called histone demethylase possible.

There are two parts to the Still Lab's brain cancer research. The first is natural product chemistry; the analytical separation chemistry and NMR analysis that Still conducts on plant extracts. The second part consists of collaborative testing on campus for anticancer activity in a "cell culture lab" that features a biosafety cabinet, a microscope for looking at cells, and an incubator to grow cells. The incubator creates an atmosphere similar to inside a human body.

"On a daily basis, we purify extracts from plants using several different types of chemical chromatography, and once pure, the chemical is elucidated with the help of the NMR spectrometer," said Still. "The spectral computer readouts tell us, for example, that this hydrogen atom is next to this carbon atom, which is next to this oxygen atom. Unambiguous elucidation of a chemical structure is a lot like solving a puzzle, but the 'pieces' are NMR experiments that tell you something about chemical scaffold as a whole."

Testing for anticancer activity in the cell culture lab is done in collaboration with Tilly Wang, professor of chemistry and biology and Department Chair at CSUDH. Wang is an expert in the area of protein biochemistry and proteomics. Her supporting role in Still's research project consists of testing pure natural product compounds for inhibition of histone demethylase.

"Our hypothesis is that treatment with natural product histone demethylase inhibitors can decrease the emergence of chemoresistance seen in current brain cancer therapy," said Wang, who was recently published in the journal Anticancer Research about this research direction.

Ultimately, Still hopes to identify a new compound structure from the plant extracts, and that his compounds will be used in synthetic lead optimization studies, an important first step in clinical cancer drug development.

"This is slow but rewarding work, because the payoff would be finding a novel lead compound that could be developed into a drug for treatment of cancer. That would be the ultimate discovery," said Still.

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