Combining computational and biochemical studies for a rationale on the anti-aromatase activity of natural polyphenols

Aromatase, an enzyme of the cytochrome P450 family, is a very important
pharmacological target, particularly for the treatment of breast cancer.
The anti-aromatase activity of a set of natural polyphenolic compounds
was evaluated in vitro. Strong aromatase inhibitors including flavones,
flavanones, resveratrol, and oleuropein, with activities comparable to
that of the reference anti-aromatase drug aminoglutethimide, were
identified. Through the application of molecular modeling techniques
based on grid-independent descriptors and molecular interaction fields,
the major physicochemical features associated with inhibitory activity
were disclosed, and a putative virtual active site of aromatase was
proposed. Docking of the inhibitors into a 3D homology model structure
of the enzyme defined a common binding mode for the small molecules
under investigation. The good correlation between computational and
biological results provides the first rationalization of the
anti-aromatase activity of polyphenolic compounds. Moreover, the
information generated in this approach should be further exploited for
the design of new aromatase inhibitors.