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 investigat...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 lites 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 IC50 values 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^(-1)3 aliphatic acid ester of substrate 2 can significantly reduce the cytotoxic activity.展开更多
文摘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 lites 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 IC50 values 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^(-1)3 aliphatic acid ester of substrate 2 can significantly reduce the cytotoxic activity.
