New developments in antitumor anthracyclines.
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-alpha-L-daunosaminyl-2'-deoxy-alpha-L-fucosyl)-4-demetho xy-adriamycinone, is presently undergoing clinical trials as a third generation antitumor anthracycline.
Arcamone
F
F
Menarini Ricerche, Rome, Italy.
Animati
F
F
Capranico
G
G
Lombardi
P
P
Pratesi
G
G
Manzini
S
S
Supino
R
R
Zunino
F
F
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000627:therapeutic use; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin