Uncommon Sugars and Their Conjugates to Natural Products

Indolocarbazoles (such as rebeccamycin, J-107088 and NSC 655649) and anthracyclines (such as doxorubicin and daunorubicin) are two important classes of anticancer drugs. Both natural and synthetic indolocarbazoles and anthracyclines contain mono-, or di-saccharides, which are critical parts of the molecules for binding to DNA or for inhibiting topoisomerases. Moreover, both natural and synthetic analogs containing disaccharides exhibit higher antitumor efficacy with unique DNA binding and topoisomerase poisoning characteristics. Thus, varying the uncommon sugar structure of indolocarbazole and anthracycline drugs will provide insightful information on the Structure-Activity Relationship (SAR) of topoisomerase I & II poisoning and DNA binding, and will potentially produce analogs for overcoming drug resistance in cancer therapy.