title: Regio- and stereo-selective hydroxylations of ingenane diterpenoids by Mortierella ramanniana and Gibberella fujikuroi.
abstract: The regio- and stereo-selective hydroxylations of two ingenane diterpenoids, 20-deoxyingenol (1) and 13-oxyingenol dodecanoat (2), by the filamentous fungi Mortierella ramanniana and Gibberella fujikuroi were investigated in the present study. Four undescribed metabolites (3-6) of substrate 1 and two undescribed metabolites (7 and 8) of substrate 2 were isolated. All the metabolites were identified as hydroxylated ingenane derivatives by extensive NMR and HR-ESI-MS data analyses. All the biotransformed compounds and the substrates were evaluated for their cytotoxicities against three human cancer cell lines, including human colon cancer Caco-2, breast cancer MCF-7, and adriamycin (ADM)-resistant MCF-7/ADM cell lines. All ingenane alcohols (1, and 3-6) displayed no significant cytotoxic activities. The substrate 13-oxyingenol dodecanoat (2) showed moderate cytotoxicity with IC50values being 35.59 ± 5.37 μmol·L-1(Caco-2), 24.04 ± 4.70 μmol·L-1(MCF-7), and 22.24 ± 5.19 μmol·L-1(MCF-7/ADM). However, metabolites 7 and 8 displayed no significant cytotoxicity. These results indicated that the hydroxylation at the C-13 aliphatic acid ester of substrate 2 can significantly reduce the cytotoxic activity.
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Yi-Qing
authors.initials: YQ
authors.lastname: Wu
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: chengzhh@fudan.edu.cn.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Cheng
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism; D001711:Biotransformation; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000737:chemistry* / Q000378:metabolism*; D005874:Gibberella / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D015394:Molecular Structure; D020094:Mortierella / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; C530110:ingenane
keywords: Diterpenoid; Gibberella fujikuroi; Hydroxylation; Ingenane; Microbial transformation; Mortierella ramanniana