Plant extract inspires new chemistry and new early lead against triple-negative breast cancer

Chemists at Emory University invented a reaction to streamline the total synthesis of a compound, phaeocaulisin A, extracted from a plant used for centuries in traditional Chinese medicine. In laboratory dish experiments conducted with biologists at Winship Cancer Institute  of Emory University, the researchers showed the compound’s efficacy against HER2-positive breast cancer cells and triple-negative breast cancer cells. An analogue of the compound the chemists constructed boosted this efficacy. 

“We not only efficiently replicated a complex natural product,” says Mingji Dai, Emory professor of chemistry. “We also improved upon it by turning it into a more potent compound.”

The Journal of the American Chemical Society published the work, led by Dai and Yong Wan, professor of pharmacology and chemical biology at Emory School of Medicine and director of basic research for the Glenn Family Breast Center at Winship Cancer Institute.

Phaeocaulisin A is an extract from Curcuma phaeocaulis, a flowering plant in the ginger family native to Asia with various uses in traditional medicine. 

“It is only the first step in a long process,” Wan says, “but the new analogue of phaeocaulisin A we have reported shows promising efficacy against triple-negative breast cancer cells, which are very aggressive and challenging to deal with.”

More years of research and testing, Wan explains, first in animal models, are required to further evaluate the compound and determine its potential as a therapeutic treatment.

Meanwhile, the new chemical process offers another tool for constructing complex molecules.

“The icing on the cake,” Dai says, “is that that the chemical reaction we invented holds potential for widespread use in organic chemistry to make many other compounds for drug discovery.”

First author of the study is Chang Liu, who did the work as an Emory PhD student in chemistry in Dai’s lab and has since graduated. Co-authors are Mingyu Zhang, a PhD student in chemistry, and Lidan Zeng, a post-doctoral fellow in Wan’s lab.