Anticancer Plant Natural Products

    Many plant natural products display anticancer or other biological activity in vitro and in
vivo; however, many of these compounds are polyphenolic and therefore prone to non-
specific effects and extensive phase 2 metabolism. Our efforts to address these
limitations focus on developing bio-isosteres for the polyphenolic moieties in the natural
products to afford more selective and metabolically stable analogs. These efforts
generally begin with efficient total syntheses, providing sufficient supplies of natural
products and analogs for mechanistic studies.  These studies often identify promising
targets and superior analogs that may be exploited in the search for new antibacterial
and antitumor agents with increased selectivity and potency.

Our current efforts focus on the following plant natural products:

• The novel, 1,5-diarylpent-1-en-4-yne rooperol, derived from African potato
(Hypoxis hemerocallidea).
• The bee propolis-derived caffeic acid phenethyl ester (CAPE).

For additional information, see the following representative publications:

• Kerwin, S. M.; Cha, J. “A concise synthesis of rooperol and related 1,5-
diarylpent-1-en-4-ynes” Tetrahedron Lett. 2014, 55, 137-141.
• Yang, J.; Bowman, P. D.; Kerwin, S. M.; Stavchansky, S. “Development and
validation of an LCMS method to determine the pharmacokinetic profiles of caffeic
acid phenethyl amide and caffeic acid phenethyl ester in Sprague-Dawley rats”
Biomed. Chromatogr. 2014, 28, 241-246.
• Li, J.; Kaoud, T. S.; LeVieux, J.; Gilbreath, B.; Moharana, S.; Dalby, K, N.;
Kerwin, S. M. “A fluorescence-based assay for p38 docking site binders:
Identification of the Hypoxis natural product rooperol as a novel p38 kinase
inhibitor” ChemBioChem, 2013, 14, 66–71.