New iantherans from the marine sponge Ianthella quadrangulata: novel agonists of the P2Y(11) receptor.
Three new iantherans, iso-iantheran A (1), 8-carboxy-iso-iantheran A (2), and iso-iantheran B (4) were isolated together with two further new brominated tyrosine-derived metabolites 5 and 6 from the polar extract of the Australian marine sponge Ianthella quadrangulata. Structures were elucidated on the basis of extensive spectral analysis. The dimeric benzofuran skeleton including a 2,3-dihydroxy-1,3-butadiene disulfate moiety found in 1, 2, and 4 is a unique feature of iantherans and to date only described for iantherans A and B. Iso-iantheran A (1) and 8-carboxy-iso-iantheran A (2) exhibited agonist activity at P2Y11 receptors with EC50 values of 1.29 muM and 0.48 muM, respectively. Compound 2 showed some selectivity for P2Y11 over P2Y1 and P2Y2 receptors. Compounds 1 and 2 represent a new structural type for the development of P2Y11 receptor agonists.
Greve
Hendrik
H
Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, D-53115 Bonn, Germany.
Meis
Sabine
S
Kassack
Matthias U
MU
Kehraus
Stefan
S
Krick
Anja
A
Wright
Anthony D
AD
König
Gabriele M
GM
D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011161:Porifera / Q000737:chemistry*; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D013329:Structure-Activity Relationship; D013463:Sulfuric Acid Esters / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
C525463:8-carboxy-iso-iantheran A; D001572:Benzofurans; D008024:Ligands; C109734:P2RY11 protein, human; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D013463:Sulfuric Acid Esters; C525461:iso-iantheran A; C525462:iso-iantheran B; D014443:Tyrosine; D002118:Calcium