Bioactive natural products

• Main Author: Woods, Katherine B.
• Language: English
• Published: University of British Columbia 2010
• Online Access: http://hdl.handle.net/2429/26234

Montbretins A-E were isolated from the corms of Crocosmia sp., an invasive perennial plant. The montbretins are inhibitors of human pancreatic α-amylase (HPA). Montbretin A (2- 30) is a competitive inhibitor of HPA with a K₁ of 1.3 nM. The activity of the other family members varied significantly and provided structure-activity information. Saturation Transfer Difference (STD) NMR spectroscopy was used to determine that the caffeic acid region of the montbretins is important for binding. HPA is involved in the breakdown of complex carbohydrates; inhibition of this enzyme could help with regulation of blood sugar levels after a meal. In the lungs of cystic fibrosis patients, the activation of Toll-Like Receptor 5 (TLR5) in the presence of flagellin leads to inflammation and obstruction. Girolline (3-1), a known alkaloid, was isolated from a Phonpeian sponge following potent inhibition of the flagellin initiated TLR5 activation. No activity was observed in any synthetic analogues of girolline. The massacreones are a new family of ecdysteroids isolated from an unidentified Dominican cnidarian. The extract of the cnidarian had good TLR5 activity, but the massacreones – namely massacreone A (3-25) and massacreone B (3-26) have only moderate activity and a small window of activity before they are toxic. The algal pigment caulerpin (4-29) was isolated from Caulerpa sp. as a compound showing good activity in a yeast growth restoration assay designed to identify inhibitors ofhuman indoleamine-2,3-dioxygenase (IDO). Caulerpin did not show any activity in a free enzyme IDO assay. IDO is involved in immune escape, which prevents the immunological rejection of tumors.