Microbial transformations of natural antitumor agents: use of solubilizing agents to improve yields of hydroxylated ellipticines

Abstract

Aromatic hydroxylation of the antitumor alkaloid ellipticine by Aspergillus alliaceus results in the formation of both 8- and 9-hydroxyellipticines. Experiments designed to increase yields of microbial hydroxylation focused on enhancing the water solubility of ellipticine in aqueous fermentation media by use of wetting agents or solubilizing polymers, or both. Yields of hydroxylated metabolites were determined by high-performance liquid chromatography with the use of a mu-Bondapak-phenyl column and a mobile phase of acetonitrile--0.1% (NH4)2CO3 (1:1). Polyvinylpyrrolidone (molecular weight, 40,000) and polyoxyethylated vegetable oil (Emulphor 620) increased the water solubility of ellipticine and the yield of hydroxylated metabolites.