Quantum Chemical Study of the Relationships between Electronic Structure and Corticotropin-Releasing Factor 1 Receptor Binding Inhibition by a Group of Benzazole Derivatives

Abdussalam, Abubakar; Gómez-Jeria, Juan S.

doi:10.18576/jpac/050101

Quantum Chemical Study of the Relationships between Electronic Structure and Corticotropin-Releasing Factor 1 Receptor Binding Inhibition by a Group of Benzazole Derivatives

Document Type : Original Article

Authors

¹ Department of Pure and Industrial Chemistry, Bayero University, Kano, P.M.B. 3011, Kano, Nigeria.

² Quantum Pharmacology Unit, Department of Chemistry, Faculty of Sciences, University of Chile. Las Palmeras 3425, Santiago 7800003, Chile.

10.18576/jpac/050101

Abstract

In this paper, we report the results of a study to find the relationships between electronic structure and corticotropin-releasing factor 1 receptor binding inhibition using the formal Klopman-Peradejordi-Gómez (KPG) method after full geometry optimization within the density functional theory (DFT) at the B3LYP/6-31g(d,p) level for a group of benzazole derivatives. Statistically significant equations were obtained. Interestingly, following the complete evaluations of the various electronic contributions of the individual molecular orbital (MO) descriptors to the binding inhibition of the benzazoles molecules investigated. The results demonstrate that the electronic interaction between the benzazole derivatives and the receptor is orbital-controlled. On the basis of the results obtained, we proposed a partial 2-dimensional pharmacophore with the contributing substituents properly positioned at the relevant molecular positions. The structural features of the proposed partial pharmacophore have the tendency to enhance its binding interaction with the receptor. The molecule-receptor interaction of the benzazoles studied herein is very complex in agreement to the high selectivity that the receptors must show to preserve the integrity of the biological system in which they are implanted.

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