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glucose transport with the tribenzoyl derivative 2f showing >99%
inhibition of glucose transport. This compound also showed the
highest level of cell growth inhibition at ꢀ60%. By analyzing all
data in Table 2, it was found that the linear correlation coefficient
R = 0.817 (R2 = 0.667), indicating that approximately 2/3 (66.7%) of
the inhibitory activity of cancer cell growth came from the inhibi-
tory activity of basal glucose transport.
In general, the presence of a hydroxy group at the 3-position of
the pendant benzoyl group is important for both inhibitions of glu-
cose transport and cancer cell growth. This 3-hydroxy group can be
attached to a chloro- or fluoro-substituted core benzene ring or be
part of a tribenzoyl system. Unsubstituted or electron-donating
substituents lead to significant decreases in the inhibition of glu-
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Given that our compounds are phenolic esters and hydrolysis
may be facile we examined a few select hydrolysis products (8,
6c, 10, 11, and 12) for glucose uptake inhibition activity. As shown
in Figure 2, none of these compounds had any glucose uptake inhi-
bition activity. Similarly, none of these compounds showed any
activity in anticancer screens (data not shown).
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In summary, we have successfully synthesized a library of muti-
phenolic ester compounds as novel inhibitors of basal glucose
transport and anticancer agents with a potential new target, basal
glucose transport. Further studies to confirm the mechanism of ac-
tion and optimize these compounds are ongoing.
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Acknowledgments
26. Melstrom, L. G.; Salabat, M. R.; Ding, X. Z.; Milam, B. M.; Strouch, M.; Pelling, J.
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We thank the National Science Foundation for support through
a Partnership for Innovation Grant (EHR-0227907) and Ohio Uni-
versity for support through the BioMolecular Innovation and Tech-
nology project.
References and notes
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