COMPUTER-AIDED DESIGN OF POTENTIAL AROMATASE INHIBITORS BASED ON 1,2,4-TRIAZOLE DERIVATIVES
https://doi.org/10.29235/1561-8323-2018-62-3-281-292
Abstract
Computer-aided design of the high-affinity inhibitors of aromatase based on 1,2,4-triazole derivatives was performed by molecular modeling tools. The potential biological activity of the designed compounds was evaluated by molecular docking and quantum chemistry calculations. As a result, six hits that form a coordinate bond with an iron atom of an enzyme hem and effectively interact with its substrate-binding site were identified. The intermolecular interactions appearing in the structural complexes of these ligands with aromatase were analyzed 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.
About the Authors
A. M. Andrianov
Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus.
Russian Federation
Russian Federation
Andrianov Alexander Mikhailovich – D. Sc. (Chemistry), Chief researcher.
5/2, Kuprevich Str., 220141.
G. I. Nikolaev
United Institute of Informatics Problems of the National Academy of Sciences of Belarus.
Russian Federation
Russian Federation
Nikolaev Gregory Igorevich – Postgraduate student.
6, Surganov Str., 220072, Minsk.
I. A. Kashyn
United Institute of Informatics Problems of the National Academy of Sciences of Belarus .
Russian Federation
Russian Federation
Kashyn Ivan Aleksandrovich – Ph. D. (Chemistry), Senior researcher.
6, Surganov Str., 220072, Minsk.
Yu. V. Kornoushenko
Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus
Russian Federation
Russian Federation
Kornoushenko Yury Valerievich – Ph. D. (Chemistry), Senior researcher.
5/2, Kuprevich Str., 220141, Minsk.
S. A. Usanov
Institute of Bioorganic Che mistry of the National Academy of Sciences of Belarus
Russian Federation
Russian Federation
Usanov Sergey Aleksandrovich – Corresponding Member, D. Sc. (Chemistry), Professor.
5/2, Kuprevich Str., 220141, Minsk.
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