Abstract
The non-selective classification refers to those beta-blockers capable of blocking both β1 and β2 receptors with equivalent efficacy. All of these beta-blockers consist of an aryloxypropanolamine side chain linked to an aromatic or heteroaromatic ring. Each of these drugs possesses at least one chiral center, and high degree of enantioselectivity in binding to beta-adrenergic receptor. In this research, ab initio method with 6-31G* basis set was employed for investigation of correlation between optimized geometry and biologically active configuration on both enantiomers of Timolol, Nadolol, Bunolol, and Propranolol. These calculations show higher stabilities for (S)-enantiomer compared with (R)-antipode, for each stereoisomer. Also, torsion angles around the N2C3C4O5 bond confirm that (S)- and (R)-Propranolol have the lowest and highest dihedral angles related to other non-selective beta-blockers, respectively. Furthermore, the (S)-enantiomers of beta-blockers reveal the more negative natural charges for oxygen atom in hydroxyl as well as nitrogen atom in aryloxypropanolamine group than related (R)-enantiomer.
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Acknowledgments
This research was partially supported by a grant from Pharmaceutical Research Network, Tehran, Iran and Pharmaceutical Sciences Research Center of Mazandaran University of Medical Sciences, Sari, Iran. The authors gratefully acknowledge the financial support of this study by the Mazandaran University of Medical Sciences ‘‘Professor’s projects funds’’ and “Pharmaceutical Research Network of Iran”.
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Bekhradnia, A.R., Ebrahimzadeh, M.A. Theoretical study on some non-selective beta-adrenergic antagonists and correlation to their biologically active configurations. Med Chem Res 21, 2571–2578 (2012). https://doi.org/10.1007/s00044-011-9781-3
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DOI: https://doi.org/10.1007/s00044-011-9781-3