DNA complexing antibiotics: daunomycin, adriamycin and their derivatives

Abstract

9-Acetyl-4-methoxy-7,8,9,11-tetrahydroxy-6,7,9,11-tetrahydroxy-o-(3'-amino-2',3',6'-trideoxy-alpha-L-lyxohexopyranoside) (daunomycin, daunorubicin, NSC-82 131, Daunoblasin), 14-hydroxy-daunorubicin (adriamycin, doxorubicin, NSC-123 127, Adriblastin), dihydrodaunomycin, their aglycones and other related compounds represent the group of S. peucetius derived antibiotics. The biosynthetic glycosides as well as some semisynthetic analogues or derivatives form strong complexes with double stranded DNA, which can be understood in terms of the known intercalation model. A clear relationship is found between the complex forming ability and the biological activity of the different compounds. The structure and configuration of the sugar moiety appear of primary importance for the stabilization of the complex and, therefore, for action. A class of side chain derivatives, namely adriamycin 14-0-esters, looks promising. Different tissue distribution of such derivatives may result in new useful anticancer drugs.