Abstract. Computer-aided design of the high-affinity inhibitors of aromatase based on 1,2,4-triasole derivatives was performed by molecular modeling tools. Potential biological activity of the designed compounds was evaluated by molecular docking and quantum chemistry calculations. As a result, nine hits that form a coordinate bond with the iron atom of the enzyme hem and effectively interact with its substrate-binding site were identified. Analysis of intermolecular interactions appearing in the structural complexes of these ligands with aromatase was carried out and the enthalpies of their formation were calculated. Based on the data obtained,   the identified compounds were suggested to present good scaffolds for the development of novel effective drugs against breast cancer. 

 

Key words: aromatase, computer-aided drug design, molecular docking, quantum chemistry, aromatase inhibitors, breast cancer.