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cytotoxicity but were less active than paclitaxel and cephalomannine in most cases
and better than etoposide. Some dimers showed a little enhancement in cytotoxicity
against drug-resistant tumor cells, compared with both precursors. In topoisomerase
assays, two paclitaxel conjugates are active topo II inhibitor in vitro and intracel-
lular poisons.
152
Shi et al. also prepared conjugates of paclitaxel and camptothecin
through amino acid and imine linkage, and they found that the conjugates' activities
were distinct from either the two drugs alone or a simple 1:1 mixture of the two
drugs. Whereas most conjugates were usually less active, 102a-c were more active
than paclitaxel against HCT-8.
153
O
AcO
NHBoc
O
O
O
N
CH
n
Ph
O
OH
N
HO
O
BzO
N
AcO
O
HO
O
102a
n=2
102b
n=3
102c
n=5
Sometimes natural taxanes or synthetic taxoids exhibited unexpected cytotoxici-
ties, which may provide new clues for SAR. Because m-azido baccatin III 103 was
found to be almost as comparably active as paclitaxel, 7-deoxy-9,10-O-acetylbac-
catin 104 was prepared from taxinine 105, a plain and abundant inactive taxane from
T. cuspidata. Both 104a and 104b were found to be inactive (IC
50
at 10
5
M level).
154
OAc
O
O
O
OH
HO
O
HO
H
O
O
O
O
A
cO
AcO
O
O
N
3
R
104a
R=N
3
104b
R=Cl
103
OAc
OAc
O
AcO
O
Ph
O
105
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