ABSTRACT
Anthracycline aminoglycosides represent a wide class of antibiotics obtained by submerged aerobic fermentation of different microorganisms belonging to the genus Streptomyces and are called anthracyclines, because the aglycone moiety is a tetracyclic system bearing an anthraquinone chromophore.1 The anthracyclines are microbial metabolites belonging, from the biogenetic standpoint,
16.1Introduction .......................................................................................................................... 383 16.2Development of the Anthracycline Drugs ............................................................................ 385
16.2.1Daunorubicin ............................................................................................................ 385 16.2.2Doxorubicin .............................................................................................................. 385 16.2.3Second-Generation Antitumor Anthracyclines ........................................................ 385
16.3Mechanism of Action............................................................................................................ 386 16.3.1DNA Complex and Topoisomerase II Poisoning ...................................................... 386 16.3.2Natural and Acquired Resistance to Anthracyclines ................................................ 387 16.3.3Cardiotoxicity ........................................................................................................... 388
16.4Synthesis of the Drugs .......................................................................................................... 388 16.4.1Doxorubicin .............................................................................................................. 388 16.4.2Epirubicin ................................................................................................................. 388 16.4.3Idarubicin .................................................................................................................. 388
16.5Medicinal Chemistry of Antitumor Anthracyclines............................................................. 389 16.5.1Analogs Modiœed in the Aglycone Moiety .............................................................. 389
16.5.1.1Deoxyderivatives ........................................................................................ 389 16.5.1.2Fluoroderivatives .......................................................................................390
