title: Novel drimane sesquiterpene esters from Aspergillus ustus var. pseudodeflectus with endothelin receptor binding activity.
abstract: A series of novel drimane sesquiterpene esters (1-6) was isolated from fermentations of Aspergillus ustus var. pseudodeflectus and their structures elucidated by spectroscopic methods including the HMQC, HMBC and INADEQUATE NMR experiments. The major component of the fermentation, 1, was (2'E,4'E,6'E)-6-(1'-carboxy-2',4',6'-trien)-9-hydroxydrim-7-ene-11 ,12-olide. Compounds 1, 2, 3 and 5 exhibited endothelin receptor binding inhibitory activity against rabbit endothelin-A and rat endothelin-B receptors with IC50 values in the range 20-150 microM. These compounds had similar levels of activity in assays for binding to human endothelin A and endothelin B receptors. The isolation of 9,11-dihydroxy-6-oxodrim-7-ene, 7, a probable biosynthetic precursor to the drimane esters is also reported.
authors.affiliation: Xenova Ltd., Slough, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Hayes
authors.forename: S K
authors.initials: SK
authors.lastname: Wrigley
authors.forename: I
authors.initials: I
authors.lastname: Chetland
authors.forename: E E
authors.initials: EE
authors.lastname: Reynolds
authors.forename: A M
authors.initials: AM
authors.lastname: Ainsworth
authors.forename: D V
authors.initials: DV
authors.lastname: Renno
authors.forename: M A
authors.initials: MA
authors.lastname: Latif
authors.forename: X M
authors.initials: XM
authors.lastname: Cheng
authors.forename: D J
authors.initials: DJ
authors.lastname: Hupe
authors.forename: P
authors.initials: P
authors.lastname: Charlton
authors.forename: A M
authors.initials: AM
authors.lastname: Doherty
mesh_terms: D000818:Animals; D001230:Aspergillus; D002210:Caprylates / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism*; D004952:Esters / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D005285:Fermentation; D006801:Humans; D015394:Molecular Structure; D011817:Rabbits; D051381:Rats; D017466:Receptors, Endothelin / Q000378:metabolism*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism*
chemical_list: D002210:Caprylates; D004952:Esters; C534016:FF8181-A; D017466:Receptors, Endothelin; D012717:Sesquiterpenes