C. Pouget et al. / Bioorg. Med. Chem. Lett. 11 (2001) 3095–3097
3097
In conclusion, on the basis of the above findings, the
7-methoxyflavanone 1d and the 7,8-dihydroxyflavone 3c
scaffolds were selected as skeleton for the development
of flavonoid structurally-related compounds having a
balance between different anti-breast cancer activities
since these compounds were found to possess not only
antiproliferative activity against MCF-7 cells but also
aromatase inhibitory effect.8 In spite of their great anti-
proliferative activity, chalcones could not be selected in
our syntheticlead-optimization study because they were
shown to be only weak inhibitors of aromatase activity.9
However, a further evaluation of chalcones will be
undertaken, concerning the structural requirements on
B-ring for inhibition of hormone-dependent human
breast cancer cell line growth.
Table 2. Cytotoxicity of 20-hydroxychalcones
Compd
IC50 (mM)
2a
2b
2c
2d
2e
2f
28.4
16.3
22.2
26.8
18.3
20.0
>60
29.2
2g
2h
flavones tested, 7,8-dihydroxyflavone 3c was found to
be the most potent (IC50=27.5 mM) whereas the corre-
sponding flavanone 1c was inactive.
The inhibitory effects of some of the flavanones were
compared to those of corresponding 20-hydroxy-
chalcones. We noted that in all cases, 20-hydroxy-
chalcones were more potent against MCF-7 cells growth
than corresponding flavanones. Surprisingly, the most
active was the 20,40-dihydroxychalcone 2b correspond-
ing to the 7-hydroxyflavanone 1b which is inactive
against MCF-7 cells proliferation. The 20,30,40-trihy-
droxychalcone 2c was also active whereas the corre-
sponding 7,8-dihydroxyflavanone 1c had no effect on
MCF-7 cells growth. Therefore, unlike flavanones,
hydroxyl substituents on A ring of chalcones are not
critical for antiproliferative effect except hydroxylation
at position 60 since 20,60-dihydroxy-40-methoxychalcone
2g is much less active than 20-hydroxy-40-methoxy-
chalcone 2d.
Acknowledgements
The authors are grateful to the Region Limousin for its
financial support and Y. Champavier for running the
NMR spectra.
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