Microbial transformations of taxadienes and the multi-drug resistant tumor reversal activities of the metabolites

Microbial transformation of two taxadienes (1, 2) was individually investigated with two filamentous fungi, Cunninghamella echinulata CGMCC 3.3400 and Aspergillus niger CGMCC 3.1858, and two actinomycete stains, Streptomyces griseus CACC 200300 and Nocardia purpurea CGMCC 4.1182. A total of 21 products were obtained, 13 of which were new compounds. The reactions that occurred exhibited diversity, including selective hydroxylation, epoxidation, oxidation, demethylation, acetylation, deacetylation, and O-alkylation, and we have proposed plausible bioconversion routes. The results of a pharmacological evaluation showed that compound 15 displayed significant reversal of activity toward multi-drug resistant (MDR) tumor cell line A549/taxol when co-administered with paclitaxel at 10 μM. This investigation provided a useful approach to prepare new active taxane derivatives that were difficult to access by chemical means.