Publication by Pharmacy Professors Fuchs and Kinghorn Highlighted in C&E News

11/10/2015

A recent publication co-authored by two faculty members in the Division of Medicinal Chemistry and Pharmacognosy, James R. Fuchs, Ph.D. (associate professor) and A. Douglas Kinghorn, Ph.D., D.Sc. (professor and Jack L. Beal chair), was recently highlighted in Chemical & Engineering News (C&EN), the weekly magazine published by the American Chemical Society. A synopsis of the research was initially published online (Plant Used In Traditional Mayan Medicine Holds Potential Leishmaniasis Treatment | Chemical & Engineering News) last September and was linked to two C&EN news feeds: the Biological SCENE and the Organic SCENE. A shorter version of the story also appeared in print in the “From the SCENEs” section of the September 28, 2015 C&E News, a section which highlights important publications in a variety of chemistry related disciplines.Pentalinonsterol

Publication by Pharmacy Professors Fuchs and Kinghorn Highlighted in C&E News

The highlighted paper, entitled “A Novel Sterol Isolated from a Plant Used by Mayan Traditional Healers is Effective in Treatment of Visceral Leishmaniasis Caused by Leishmania donovani”, was published in the journal ACS Infectious Diseases in August (DOI: 10.1021/acsinfecdis.5b00081; vol. 1, pp. 497-506, 2015). It describes the synthesis, encapsulation, and in vivo activity of the natural product pentalinonsterol. Pentalinonsterol was originally isolated and structurally characterized in the Kinghorn lab at Ohio State from a plant that grows in the Yucatan peninsula of Mexico where it is used in traditional medicine for the treatment of leishmaniasis, a parasitic disease spread by sand flies. Although only small quantities of the compound could be effectively obtained from the plant material, it was shown to be highly effective at killing the parasites. In order to further study the antiparasitic properties of this compound, the Fuchs lab developed an efficient synthesis of pentalinonsterol, making enough of the natural product for the necessary in vitro and in vivo studies that were carried out by collaborators at Ohio State (Abhay R. Satoskar, M.D., Ph.D.) and the University of North Carolina (Kristy M. Ainslie, Ph.D., and Eric M. Bachelder, Ph.D.). In the end, the compound was shown not only to kill the parasites as demonstrated via dramatic reductions in parasite levels in infected mice, but was also observed to stimulate their immune systems to aid in fighting the infection.

In describing the research, Elizabeth R. Sharlow, a pharmacologist from the University of Virginia was quoted as saying “Pentalinonsterol could represent the next generation of small-molecule-mediated immunotherapy for visceral leishmaniasis”. Overall, the work was also referred to as “an ‘elegant translational study’ that integrates novel chemistry, traditional medicinal and natural products to address a pressing need.”

The study was funded by grants from the NIH (NAIAD) and the US Army/DOD (USAMRAA).