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References and notes
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Regioisomers 4 and 13 were built with the MOE program.
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The conformers were minimized using the MMFF94s
force field using a gradient of 0.01 kcal/mol A. The
resulting minimized structures were imported into ISIS-
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MDLMOL files. A centroid was set on the thiophene ring
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16. IC50’s values were determined singly from dose-response
curves using 11 concentrations for each compound.
Curves were fitted to data points using nonlinear regres-
sion analysis and IC50’s values were interpolated from the
resulting curves using GraphPad Prism software, version
2.0 (GraphPad Software, Inc., San Diego, CA, USA). A
positive control was included as an internal standard in
each set of experiments, and results were considered
accurate only when the IC50 value of the positive control
was within 0.45Æ0.16 mM. Similarly, IC50’s in replicons
were determined using 12 concentrations in duplicate and
data were considered accurate when IC50 of a positive
control was within 8.9Æ2.4 mM. CC50’s in Huh-7 cells
were determined from 5 concentrations in quadruplicate
and data were taken when CC50 of a positive control was
within 62Æ10 mM.