New Developments in Antitumor Anthracyclines
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- 作者：Arcamone ; Federico ; Animati ; Fabio ; Capranico ; Giovanni ; Lombardi ; Paolo ; Pratesi ; Graziella ; et. al.
- 关键词：Anthracyclines ; anticancer ; disaccharide ; MEN 10755 ; DNA-binding drugs ; topoisomerase II
- 刊名：Pharmacology and Therapeutics
- 出版年：1997
- 出版时间：November 12, 1997
- 年：1997
- 卷：76
- 期：1-3
- 页码：117-124
- 全文大小：549 K
文摘
Doxorubicin is a major anticancer agent introduced to extended clinical use in the early 1970s. The fulfillment of a wide program of analogue synthesis led to the development of the better tolerated epirubicin and of a highly potent antileukemic drug, idarubicin. In recent years, on the basis of the available information on the molecular requirements for action, a new synthetic program, coupled with target-oriented pharmacological experiments, was carried out. Various interesting derivatives, namely, the 8- and 10-fluoro compounds and the disaccharides, were obtained. The latter compounds exhibited a strong dependence of biological activity on the orientation (axial vs. equatorial) of the second sugar moiety, daunosamine. A member of this group, namely, 7-O-(4′-O-α-l-daunosaminyl-2′-deoxy-α-l-fucosyl)-4-demethoxy-adriamycinone, is presently undergoing clinical trials as a third generation antitumor anthracycline.