Chemistry Reference
In-Depth Information
useful agents for other diseases, especially as an antiparasitic agent, such as against
Schistosoma japonicum,Clonorchis Sinensis, Theileria annulatan, and Toxoplasma
gondii. In the 1970s, artemether and artesunate were confirmed to be more
active than artemisinin in both animal models.
235-237
They strongly killed the
immature worms living in mice, but praziquantel could not act. Their prevention
of the development of the mature female worms was also proved in other animal
models (rat, rabbit, and dog).
238-240
Since 1993, artemether and artesunate were
studied in randomized, double-blind, placebo-controlled trials in China
241-249
and
approved as the prevention drugs for schistosomiasis by the Chinese authorities
in 1996. Afterward, these drugs showed similar activity against S. mansoni and
S. haematobium in the laboratory studies and clinical trials in other countries.
250-253
5.6.1.3 Antitumor Activity
Some components of A. annua L., such as qinghaosu (1), artemisinin B (10), arte-
misinic acid (20), artemisitene (26), flavnoids, and other terpenoids, showed
antitumor
activities
at
varying
concentrations
against
L-1210,
P-388,
A-549,
HT-29, MCF-7, and KB in vitro.
69,254,255
In the assay of cytotoxicity of qinghaosu and related compounds against Ehrlich
ascites tumor cells, qinghaosu, artemether, arteether, and artesunate exhibited cyto-
toxicity (IC
50
12.2
29.8 mM), artemisitene 51 was more active (IC
50
6.8 mM), and
the dimer of dihydroartemisinin was the most potent (IC
50
1.4 mM).
256-258
The antitumor effect of artesunate was tested in vitro and in vivo in China.
259-261
It possessed cytotoxicity for six cell lines (IC
50
1
100 mg/mL) and antitumor
effects on human nasopharyngeal cancer (CNE2, SUNE-1) and human liver cancer
(BEL-7402) in nude mice. Recently artesunate has been analyzed for its antitumor
activity against 55 cell lines.
262
It was most active against leukemia and colon can-
cer cell lines. It is notable that no CEM leukemia sublines, which are resistant to
either
doxorubicin,
vincristine,
methotrexate,
or
hydroxyurea,
showed
cross
resistance to artesunate.
It was found that dihydroartemisinin can selectively kill cancer cells in the
presence of holotransferrin, which can increase intracellular iron concentrations,
and normal breast cells (HTB 125) and lymphocytes had nonsignificant changes.
It seems the mechanisms of anticancer action and of antimalarial activity are
similar.
263-265
The antitumor activity of N-glycoside, O-glycoside, and some dimers have been
mentioned. Recently, compound 153 was found to have antitumor activity. Addi-
tional study discovered the most active compound 154 in this series ( R
¼
p-Br,
IC
50
¼
11 nM, and 27 nM against P 388 and A 549 cell lines, respectively), but
its deoxy analog 155 is inactive.
266,267
Compound 156 yielded by coupling that
the cyanoarylmethyl group with artesunate can not show higher antitumor activity
than 154.
268
Flow cytometry data showed that these compounds caused an accumu-
lation of L1210 and P388 cells in the G1-phase of the cell cycle and apoptosis in the
P388 cells (Structure 5-24).
266-268
More studies on antitumor action of qinghaosu analogs were reported.
269,270
Search WWH ::
Custom Search