3026
S. Tapadar et al. / Bioorg. Med. Chem. Lett. 19 (2009) 3023–3026
gemcitabine,19 and thus there is an urgent need for more efficient
drugs. All HDAC inhibitors 6–15, along with the currently mar-
keted drug SAHA were tested on five pancreatic cancer cell lines
using the MTT assay. These data are provided in the Table 3. As
is apparent from these data, compound 6 nicely inhibited all the
five transformed cell lines and its IC50 values were similar to those
of SAHA. The relatively weak HDAC inhibitor 12 showed only mod-
erate activity against three of the five transformed cell lines,
namely, BxPC-3, HuPT3 and Su.86.86. In contrast, the most potent
HDAC inhibitor in this series, compound 7, only moderately inhib-
ited the five pancreatic cancer cell lines. Compound 11 failed to
show similar antiproliferative activity compared to compound 6,
although its IC50 values in the in vitro HDAC inhibitory assay are
very similar to those of 6. The weak inhibitory activities of com-
pound 7 and 11 against different pancreatic cancer cell lines might
be due to their poor cell permeability. Compounds 8–10 and 13–15
exhibited poor antiproliferative activities against all five pancreatic
cancer cell lines, which are consistent with their poor HDAC inhib-
itory activities.
by the Mayo Foundation and the Pancreatic Cancer SPORE P50
CA102701.
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Acknowledgement
This work was supported in part by gift funds from an anony-
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