Fungal transformation of isosteviol lactone and its biological evaluation for inhibiting the AP-1 transcription factor.
A number of hydroxylated diterpenoids were obtained from the microbial transformation of isosteviol lactone (4alpha-carboxy-13alpha-hydroxy-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactone) (2) with Mucorrecurvatus MR 36, Aspergillusniger BCRC 31130, and Absidiapseudocylindrospora ATCC 24169. Incubation of 2 with M. recurvatus and Asp.niger led to isolation of seven known compounds (1 and 3-8). Incubation of 2 with Abs. pseudocylindrospora produced 5 and six previously unreported compounds (9-14). The structures of these isolated compounds were deduced by high-field NMR techniques ((1)H, (13)C, DEPT, COSY, NOESY, HSQC, and HMBC), and those of 9 and 11 were further confirmed by X-ray crystallographic analyses. Subsequently, the inhibitory effects on activator protein-1 (AP-1) activation in lipopolysaccharide-stimulated RAW 264.7 macrophages of all of these compounds were evaluated. Compounds 2-5, 8, 9, 11, and 12 exhibited significant inhibitory activity, while 3 was more potent than the reference compound of dexamethasone.
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
Lin
Wen-Kuang
WK
Wang
Li-Hsuan
LH
Liu
Pan-Chun
PC
Lin
Shwu-Jiuan
SJ
D000818:Animals; D002460:Cell Line; D018360:Crystallography, X-Ray; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D005658:Fungi / Q000187:drug effects*; D007783:Lactones / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D021241:Spectrometry, Mass, Electrospray Ionization; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*
D045786:Diterpenes, Kaurane; D007783:Lactones; D018808:Transcription Factor AP-1; C474284:isosteviol lactone