Syntheses and biological activities of daunorubicin analogs with uncommon sugars.
To study the effects of the sugar structure on the activity of anthracycline against cancer cells, six daunorubicin analogs containing different uncommon sugars were synthesized. Their cytotoxicities were tested against colon cancer cells by MTS assay. The results showed that the aglycon without sugar moiety has 70-100-fold lower activity against cancer cells than daunorubicin derivatives with various uncommon sugars. It suggests that the sugar structure in daunorubicin plays a critical role in determining its anticancer activity. In the compounds with various sugars, the 4'-OH of the sugar is an important determinant for their activity, while the axial-3'-substituent in the sugar interferes with the binding of daunorubicins to DNA. Therefore, 2,6-dideoxy sugars are a better choice for generating biologically active daunorubicin analogs than 6-deoxysugars, 2,3,6-trideoxysugars, or 2,3,4,6-tetradeoxysugars.
Zhu
Lizhi
L
Department of Chemistry and Biochemistry, The Ohio State University, Columbus, 43210, USA.
Cao
Xianhua
X
Chen
Wenlan
W
Zhang
Guisheng
G
Sun
Duxin
D
Wang
Peng George
PG
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure
D003630:Daunorubicin