NEW DEVELOPMENTS IN ANTITUMOR ANTHRACYCLINES

Doxorubicin is a major anticancer agent introduced to extended clinica l use in the early 1970s. The fulfillment of a wide program of analogu e 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 requiremen ts for action, a new synthetic program, coupled with target-oriented p harmacological experiments, was carried out. Various interesting deriv atives, namely, the 8- and 10-fluoro compounds and the disaccharides, were obtained. The latter compounds exhibited a strong dependence of b iological activity on the orientation (axial vs. equatorial) of the se cond sugar moiety, daunosamine. A member of this group, namely, '-deox y-alpha-L-fucosyl)-4-demethoxy-adriamycinone is presently undergoing c linical trials as a third generation antitumor anthracycline. (C) 1997 Elsevier Science Inc.