| Summary: | 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.
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