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M. Kinger et al.
at para position of the phenyl group in compound 3k
resulted in a two-fold improvement in inhibitory
activities compared with 3a, with an IC50 values of 1.5
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with an IC50 value of 22.3 M. This suggests that the
µ
4-position of the substituent on the phenyl ring is
crucial and plays an important role in the inhibitory
effect of these compounds.
Previous reports have suggested that naturally
isolated diarylheptanoids containing a prop-2-en-1-
one core moiety were able to inhibit NA in an enzyme
test (Grienke et al., 2010). The report revealed that
the two peripheral phenyl groups, with a spacer re-
presented by the heptyl chain, seemed to contribute to
NA inhibitory activity. In this study, we examined the
NA and influenza virus inhibitory activities of our
series of 1,3-diarylprop-2-en-1-one derivatives (3a-v).
We conducted a SAR study with the compounds to
determine the optimal structure and position of the
substituent for significant and specific NA inhibitory
activities. To our knowledge, this is the first demon-
stration of a small-molecule inhibitor of NA. Com-
pound 3k, with an
tion on the phenyl ring, was found to have especially
effective inhibitory activities (an IC50 value of 1.5 M).
N,N-dimethylamino at the 4-posi-
µ
The analogues that have more lipophilic groups gener-
ally showed decreased potency compared with the
corresponding, less lipophilic analogues. This would
indicate that the increase in potency of the NA inhibi-
tory activity is related to a more substantial interac-
tion with the enzyme and influenced by lipophilicity.
Jeong and co-workers also suggested that the presence
of the less lipophilic group in the B-ring of flavonoids
is essential for their potent inhibitory activity against
NA (Jeong et al., 2009). In summary, these preliminary
data demonstrate that 1,3-diarylprop-2-en-1-ones deri-
vatives might be considered as a potential therapeutic
agent in the treatment of influenza virus infections.
ACKNOWLEDGEMENTS
This work was supported by Nuclear R&D Program
from the Ministry of Education, Science and Technol-
ogy (MEST).