M.I. Zagorodnyy, O.O. Kazakova, A.S. Svintsitsky Investigation of quantum-pharmacological properties of atenolol, metoprolol, propranolol and carvedilol

The aim of the study was to investigate the mechanisms of primary pharmacological reaction of β-blockers, using quantum-chemical methods. The study of the quantum-chemical properties of molecules of
β-adrenoblockers atenolol, metoprolol, propranolol and carvedilol was performed using software GAMESOL by method of Hartry-Fok in nonempiric basis 6-31G(d). All calculations of geometric, electronic and energetic
parameters of molecules were done in the water solution. Carvedilol had a most negative charge of oxygen atom of hydroxyl group compared to atenolol, metoprolol and propranolol. Analysis of atoms distribution in the
molecules of adrenoblockers indicates about higher proton donor ability of active groups of carvedilol molecule. Carvedilol has a big brachiate N-alcyle radical and more value of surface area of hydrophobic part in comparison with other β-adrenoblockers. Carvedilol molecule has more numbers of the active groups with ability to create the hydrogen binding with active adrenoreceptor. In conclusion, more expressed pharmacological activity of carvedilol is caused by energy of intermolecular interactions in the water medium, high electron-donor capability and possibility of formation of more powerful connection with active groups of adrenoreceptors. Brachiate N-alcyle radical of carvedilol molecule contribute to interaction with hydrophobic parts of β-adrenoreceptor

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