title: Microbial transformation of isosteviol lactone and evaluation of the transformation products on androgen response element.
abstract: Two filamentous fungi, Cunninghamella bainieri ATCC 9244 and Aspergillus niger BCRC 32720, were used to investigate the biotransformation of isosteviol lactone (4alpha-carboxy-13alpha-hydroxy-13,16- seco-ent-19-norbeyeran-16-oic acid 13,16-lactone) ( 2), which was derived by reacting isosteviol ( ent-16-oxobeyeran-19-oic acid) ( 1) with m-chloroperbenzoic acid. Incubation of 2 with C. bainieri afforded metabolites 3- 6, which involved isomerization, hydroxylation, and ring cleavage reactions followed by oxidation and selective O-methylation. Incubation of 2 with A. niger afforded mono-, di-, and trihydroxylated metabolites 3, 4, and 7- 12. The structures of 3- 12 were elucidated on the basis of spectroscopic analyses, and structures 3, 4, and 6 were confirmed by X-ray crystallographic studies. Compounds 2- 6, 8- 10, and 12 were assayed as androgen agonists using an ARE (androgen response element)-mediated luciferase reporter gene assay. Compounds 3, 6, and 10 were significantly active, with 6 showing more activity than testosterone.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Bo-Hon
authors.initials: BH
authors.lastname: Chou
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Yang
authors.forename: Shwu-Fen
authors.initials: SF
authors.lastname: Chang
authors.forename: Feng-Lin
authors.initials: FL
authors.lastname: Hsu
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Lo
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Liaw
authors.forename: Pan-Chun
authors.initials: PC
authors.lastname: Liu
authors.forename: Shwu-Jiuan
authors.initials: SJ
authors.lastname: Lin
mesh_terms: D000728:Androgens; D001234:Aspergillus niger / Q000378:metabolism*; D018360:Crystallography, X-Ray; D020093:Cunninghamella / Q000378:metabolism*; D045786:Diterpenes, Kaurane / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D007783:Lactones / Q000737:chemistry* / Q000378:metabolism*; D008156:Luciferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008968:Molecular Conformation; D015394:Molecular Structure; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism
chemical_list: D000728:Androgens; D045786:Diterpenes, Kaurane; D007783:Lactones; D011944:Receptors, Androgen; C474284:isosteviol lactone; C515747:isosteviol; D008156:Luciferases