INITIAL BIOTRANSFORMATIONS OF DAUNORUBICIN TO AGLYCONES BY RAT-LIVER MICROSOMES

Abstract

Anaerobic incubations of rat liver microsomes convert [the antineoplastic drug] daunorubicin into at least 6 or 7 aglycones in the presence of reduced NADP or a reduced NADP-generating system. The partial identification of some of the aglycones is based on cochromatographs of chemically synthesized derivatives by isocratic, high-pressure liquid chromatography. The 1st major reaction is the reductive cleavage of daunorubicin to 7-deoxydaunorubicin aglycone, which is converted to another product that cochromatographs with 7-deoxydaunorubicin aglycone. The reaction follows 1st-order kinetics in a linear sequential pathway. Formation of 7-hydroxydaunorubicin aglycone is also identified as a product. Other reaction products are not yet identified.