Regio- and stereo-selective hydroxylations of ingenane diterpenoids by Mortierella ramanniana and Gibberella fujikuroi.
10.1016/S1875-5364(17)30020-1
- Author:
Yi-Qing WU
1
;
Yue CAO
1
;
Xin LIU
1
;
Zhi-Hong CHENG
2
Author Information
1. Department of Pharmacognosy, School of Pharmacy, Fudan University, Shanghai 201203, China.
2. Department of Pharmacognosy, School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: chengzhh@fudan.edu.cn.
- Publication Type:Journal Article
- Keywords:
Diterpenoid;
Gibberella fujikuroi;
Hydroxylation;
Ingenane;
Microbial transformation;
Mortierella ramanniana
- MeSH:
Antineoplastic Agents;
chemistry;
metabolism;
Biotransformation;
Cell Line, Tumor;
Diterpenes;
chemistry;
metabolism;
Gibberella;
metabolism;
Humans;
Hydroxylation;
Molecular Structure;
Mortierella;
metabolism;
Stereoisomerism
- From:
Chinese Journal of Natural Medicines (English Ed.)
2016;14(12):939-945
- CountryChina
- Language:English
-
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 IC values being 35.59 ± 5.37 μmol·L (Caco-2), 24.04 ± 4.70 μmol·L (MCF-7), and 22.24 ± 5.19 μmol·L (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.
