Microbial Transformations Of 3-Oxo-Oleanolic Acid And Its PEG-Conjugated Derivatives

3-oxo-olean-12-en-28-oic acid (3-oxo-OA), a kind of pentacyclic triterpenoid exhibits anticancer and antiangiogenic activities. But the weaker biological activities and lower water-solubility limited its application. The chemical methods are more commonly used than the biotransformated procedures for modification. The chemical methods, however, were limited to activated positions in the triterpenoid molecules. Biotransformation, which exhibits higher region-selectivity and stereo-selectivity, may contribute to new derivatives of 3-oxo-OA for the research of lead compounds. Here,3-oxo-OA was modified using both chemical synthesis and microbial transformation in order to obtain novel lead compounds.The lower water-solubility of organic compounds is one of problems of the biotransformation. The PEGylation can be used for solving the water-solubility problems in pharmaceutical research. The 3-oxo-OA was PEGylated in order that 3-oxo-OA dissolved in the zymotic fluid without any organic cosolvent, Microbial transformation of 3-oxo-OA and its PEGylation compound were performed by Aspergillus terreus 3.3935 by both the resting and growing cells. The microbial transformation conditions of 3-oxo-OA by Aspergillus terreus 3.3935 were optimized. The biotransformation of 3-oxo-OA afforded four products by growing Aspergillus terreus 3.3935, and obtained two products by resting Aspergillus terreus 3.3935. The transformation of PEGylated 3-oxo-OA afforded one product. The transformated products were derivatized.The anticancer and a-glucosidase inhibitory activity of 3-oxo-OA and its transformated derivatives were evaluated. The results showed that the ring-cleavage and the ring-expansion of A-ring did not affect the anticancer activity. But the a-glucosidase inhibitory activity greatly decreased with A-ring changing.