Microbial transformation of isosteviol lactone and evaluation of the transformation products on androgen response element.
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.
Chou
Bo-Hon
BH
Department of Medicinal Chemistry, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
Yang
Li-Ming
LM
Chang
Shwu-Fen
SF
Hsu
Feng-Lin
FL
Lo
Chia-Hsin
CH
Liaw
Jia-Horng
JH
Liu
Pan-Chun
PC
Lin
Shwu-Jiuan
SJ
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
D000728:Androgens; D045786:Diterpenes, Kaurane; D007783:Lactones; D011944:Receptors, Androgen; C474284:isosteviol lactone; C515747:isosteviol; D008156:Luciferases