Biotransformation of 20(S)-protopanaxatriol by Mucor spinosus and the cytotoxic structure activity relationships of the transformed products.

Biotransformation of 20(S)-protopanaxatriol (1) by the fungus Mucor spinosus AS 3.3450 gave 10 metabolites (2-10), of which 2-5 were previously known. On the basis of NMR and MS analyses, structures 6-10 were established as 12-oxo-23beta-hydroxyl-20(S)-protopanaxatriol (6), 20S,24R-epoxy-dammaran-3beta,6alpha,25-triol-12-one (7), 29-hydroxyl-20(S)-protopanaxatriol (8a), 12-oxo-11beta-hydroxyl-20(S)-protopanaxatriol (8b), 28-hydroxyl-20(S)-protopanaxatriol (9) and 12-oxo-20(S)-protopanaxatriol (10). The biotransformation kinetics of 1 has been investigated and a possible biotransformation pathway proposed. The in vitro cytotoxic activities of metabolites against three human cancer cell lines were determined by the MTT method; compounds 8a, 9 and 10 had more potent inhibitory effects against HL-60 cell line than the substrate.