np9b00551_si_001.pdf (1.54 MB)
Anti-prion Butenolides and Diphenylpropanones from the Australian Ascidian Polycarpa procera
journal contribution
posted on 2019-08-22, 15:09 authored by Laurence
K. Jennings, Luke P. Robertson, Kathryn E. Rudolph, Alan L. Munn, Anthony R. CarrollA library of 500 Australian marine
invertebrate extracts was screened
for anti-prion activity using a yeast-based assay, and this resulted
in an extract from the ascidian Polycarpa procera showing potent activity. Purification of this extract led to the
isolation of six new butenolide metabolites, the procerolides 1–4 and two related diphenylpropanones,
the procerones 5 and 6, as the bioactive
components. The structures of 1–6 were elucidated from the analysis of 1D/2D NMR and MS data, and
their absolute configurations determined from comparison of experimental
and computed ECD data. Compounds 1–6 were tested for anti-prion activity in a yeast-based assay, and 1 and 5 displayed potent bioactivity (EC50 of 23 and 29 μM, respectively) comparable to the potently
active anti-prion compound guanabenz. The procerolides and procerones
are the first anti-prion compounds to be reported from ascidians,
indicating that ascidians may be an untapped source of new lead anti-prion
compounds.