Chemistry Reference
In-Depth Information
H
3
C
O
O
HO
O
OH
O
OH
O
O
O
O
O
O
O
O
H
3
CO
OCH
3
H
3
CO
OCH
3
OCH
3
OH
31
R = H
33
R = PO
3
H
2
30
S
O
O
HO
O
O
OH
O
O
OH
O
R
OH
O
O
O
CH
3
O
O
OH
O
O
H
3
CO
OCH
3
OH
HO
NH
2
34
Daunorubicin; R = CH
3
35
Doxorubicin; R = CH
2
OH
Figure 13.9
Structures of podophyllotoxin, etoposide, teniposide, etopophos, daunoru-
bicin, and doxorubicin.
32
(
38
) as inhibitors of components of the eukaryotic cell cycle and of protein
kinase C. Although these compounds are related structurally to rebeccamycin,
they have very different mechanisms of action, in that they are highly potent but
entirely nonselective inhibitors of protein kinases. UCN-01 has entered Phase I/II
clinical trials against a variety of cancers, including leukemias, lymphomas, vari-
ous solid tumors, melanoma, and small-cell lung cancer. Its clinical development
has been hampered by its high binding to human plasma proteins (60, 61).
