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J.-C. Jung et al. / Bioorg. Med. Chem. Lett. 14 (2004) 5527–5531
Table 3. In vitro antitumor activityof 4-hydroxycoumarin derivatives 19a–c and 20a–i
Compounds
IC50 (lM)a
A549b
SK-OV-3
SK-MEL-2
XF-498
HCT-15
19a
19b
9.18
8.13
5.69
5.74
8.54
8.51
6.73
6.59
8.59
6.71
20b
19c,20a,20c–i
Etoposidec
1.83
1.80
2.05
1.36
1.31
>10
>10
>10
>10
>10
1.06
3.46
4.13
3.14
1.45
a IC50: concentration which produces 50% inhibition of proliferation after 72h of incubation.
b Cell lines: A549: human lung tumor, SK-OV-3: human ovarian tumor, SK-MEL-2: human melanoma tumor, XF 498: human brain tumor, HCT-
15: human colon tumor.
c Etoposide: compared material.
20b is superior to etoposide against human tumor cell
lines tested. The IC50 values of compound 20b were
1.83, 1.80, 2.05, and 1.36lM against the SK-OV-3,
SK-MEL-2, and XF498, whereas those of etoposide
were 3.46, 4.13, and 3.14lM. When the O-tri-
fluorobenzyl group was used as substituent at C-3 (com-
pounds 20c, 20f, and 20i in Table 2), the resulting
compounds showed significantlyreduced antitumor
activity. Interestingly, the compounds with the relatively
small C-6 alkyl substituent (19a and 20b) exhibited sim-
ilar or higher in vitro cytotoxicities when compared to
compounds where one of the substituent was a large
alkyl side chain (compounds 19b–c and 20e).
Acknowledgements
This work has been supported byChungbuk National
UniversityGrant in 2004. We would like to thank Dr.
KimberlyK. Vines for consideration of this manuscript.
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Measurement of antitumor activity: Human cancer cell
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In conclusion, a simple preparation of 4-hydroxycouma-
rin derivatives has been described. The synthetic strate-
gies involve the use of well-known Friedel–Crafts
acylation, Reformatsky reaction, and 1,4-Michael addi-
tion. Compounds 19a and 19b moderate activityin the
five cell lines tested. We have found that the compound
20b exhibited the most potencywith IC 50 values ranging
from 1.31 to 2.05lM.