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J Med Chem. 2008 Mar 13;51(5):1126-35. doi: 10.1021/jm701107h. Epub 2008 Feb 14.

Novel sulfonanilide analogs decrease aromatase activity in breast cancer cells: synthesis, biological evaluation, and ligand-based pharmacophore identification.

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College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.


Aromatase converts androgens to estrogens and is a particularly attractive target in the treatment of estrogen receptor positive breast cancer. Previously, the COX-2 selective inhibitor nimesulide and analogs decreased aromatase expression and enzyme activity independent of COX-2 inhibition. In this manuscript, a combinatorial approach was used to generate diversely substituted novel sulfonanilides by parallel synthesis. Their pharmacological evaluation as agents for suppression of aromatase activity in SK-BR-3 breast cancer cells was extensively explored. A ligand-based pharmacophore model was elaborated for selective aromatase modulation (SAM) using the Catalyst HipHop algorithms. The best qualitative model consisted of four features: one aromatic ring, two hydrogen bond acceptors, and one hydrophobic function. Several lead compounds have also been tested in aromatase transfected MCF-7 cells, and they significantly suppressed cellular aromatase activity. The results suggest that both genomic and nongenomic mechanisms of these compounds are involved within the aromatase suppression effect.

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