Fungal transformation of isosteviol lactone and its biological evaluation for inhibiting the AP-1 transcription factor

摘要

A number of hydroxylated diterpenoids were obtained from the microbial transformation of isosteviol lactone (4 alpha -carboxy-13 alpha -hydroxy-13,16-seco-ent-19-norbeyeran-16-oic acid 13,16-lactone) ( 2) with Mucor recurvatus MR 36, Aspergillus niger BCRC 31130, and Absidia pseudocylindrospora 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 ( super(1)H, super(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.