Aselacins, novel compounds that inhibit binding of endothelin to its receptor. I. The producing organism, fermentation and biological activity.
A radioligand test to detect inhibitors of endothelin-1 binding to its receptors in bovine atrial and porcine cerebral membranes was used to screen fungal metabolites from stationary fermentations. Inhibitory activity, observed in culture extracts of two Acremonium species, led to the discovery of aselacins A, B and C. Aselacin A inhibits binding to both membrane fractions with IC50s of approximately 20 micrograms/ml.
Jackson
M
M
Pharmaceutical Products Research and Development, Abbott Laboratories, Abbott Park, IL 60064.
Burres
N S
NS
Karwowski
J P
JP
Alder
L A
LA
Humphrey
P E
PE
Kohl
W L
WL
McAlpine
J B
JB
D000164:Acremonium / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism*; D005285:Fermentation; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000096:biosynthesis / Q000494:pharmacology*; D013552:Swine; D047630:Depsipeptides; D055666:Lipopeptides
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007211:Indoles; D010456:Peptides, Cyclic; C088523:aselacin A; D047630:Depsipeptides; D055666:Lipopeptides; C088524:aselacin B; C088525:aselacin C