The quantitative structure-activity relationship (QSAR) of a series of 19-substituted androstenedione analogs as aromatase inhibitors was investigated by molecular dynamics and quantum chemical AM1 method. The results show that there are spatial requirement and hydrophobic effect in the interaction between P450 aromatase and 19-substituted inhibitors. The results also show that most of these compounds are excellent electron donors, and the main electron donating group of the compounds is around the sulfur atom of 21-position. These results may provide valuable clues for searching potential aromatase inhibitors with high affinities.

Key words: ENZYME, INHIBITOR, androstenedione, QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP, molecular dynamics