A new class of semisynthetic anthracycline glycoside antibiotics incorporating a squaric acid moiety.
Treatment of the squaric acid amide esters (7, 9) of anthracycline glycoside antibiotics with aliphatic and aromatic primary and secondary amines, amino acids, peptides and aminodeoxy sugars furnished the new asymmetric diamides 16-19, 25-30, 32, 34 and 38-40 in stereoselective reactions which do not require protecting group-manipulations. The IC50 = 0.12 microM value measured for daunorubicin (1) on human leukemia (HL-60) cells is comparable to those obtained for the daunomycin-L-leucyl squaric acid diamide (30, IC50 = 0.18 microM) and the corresponding D-galactosamine derivative (40, IC50=0.22 microM).
Sztaricskai
Ferenc
F
Research Group for Antibiotics of the Hungarian Academy of Sciences, and Department of Pharmaceutical Chemistry, University of Debrecen, Debrecen, Hungary. sztarife@delfin.klte.hu
Sum
Anita
A
Roth
Erzsébet
E
Pelyvás
István F
IF
Sándor
Szabolcs
S
Batta
Gyula
G
Herczegh
Pál
P
Reményi
Judit
J
Miklán
Zsanett
Z
Hudecz
Ferenc
F
D018943:Anthracyclines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D003503:Cyclobutanes / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D003503:Cyclobutanes; C030042:squaric acid