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Biological Chemistry

Immunosuppressants Pack Powerful Punch

Natural Products: Researchers identify triterpenoids with unprecedented ring system

by Stephen K. Ritter
January 8, 2015 | A version of this story appeared in Volume 93, Issue 2

Phainanoid F, with its spirocyclic groups highlighted in red, is the most powerful of the newly discovered immunosuppressants.
A line structure of a phainanoid.
Phainanoid F, with its spirocyclic groups highlighted in red, is the most powerful of the newly discovered immunosuppressants.

Whether they’re picking apart an ancient Chinese herbal medicine or a backwoods home remedy from the southern Appalachians, chemists are interested in identifying bioactive molecules in various cures and determining how they work. Now and again the scientists come across something interesting.

A research team led by Jian-Min Yue of the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences has uncovered six new compounds, called phainanoids A–F, notable for a never-before-seen ring system. The researchers found that the bioactive molecules have the potential to knock down the body’s immune system, which could help prevent organ transplant rejection and immunity-associated disorders such as multiple sclerosis (J. Am. Chem. Soc. 2014, DOI: 10.1021/ja511813g).

Yue and coworkers came across the phainanoids while studying Phyllanthus hainanensis, a chemically uncharacterized member of a group of some 700 flowering plants scattered throughout tropical regions. Some Phyllanthus species are used in traditional Chinese medicine and Ayurvedic medicine in India for treating infections, diabetes, and hepatitis B.

The right side of the phainanoid ring system is structurally similar to a rare group of dichapetalin-type triterpenoids that contain a spirocyclic lactone. The left side, however, is unprecedented in containing a second spirocyclic group—a benzofurancyclobutanone.

After characterizing the phainanoids by spectroscopic and chemical methods, including X-ray crystallography, the Shanghai researchers tested the compounds for their ability to impede proliferation of white blood cells (lymphocytes) from mice. They found that the immunosuppressive properties exceed those of cyclosporin A, a drug often given to transplant patients and people with rheumatoid arthritis.

“The nanomolar values effective against both T and B cells are certainly impressive and unexpected,” notes A. Douglas Kinghorn, editor-in-chief of the Journal of Natural Products and a professor at Ohio State University, whose research group studies Phyllanthus anticancer compounds. “It does seem as if compounds from plants in the genus Phyllanthus do have potential in modulating the immune system in humans.”



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