Density Functional Study of Inhibitor Effect of Benzoxazepin Derivatives on Phosphoinositide-3-Kinase Delta (PIK3δ)

Phosphoinositide-3-kinase delta (PI3Kδ) is a lipid kinase that has been implicated to play a key role in a variety of immune-mediated disorders such as asthma, rheumatoid arthritis and other inflammatory disease [1]. Inhibitor is a substance that decreases the rate or stops completely a chemical reaction. A novel selective benzoxazepin inhibitor of PI3Kδ has been discovered [2]. In this study, the interaction of benzoxazepin derivatives with PIK3δ was evaluated using density functional theory (DFT) method. DFT calculations at the B3lyp/6-31G* level were performed to investigate the interaction properties and molecular descriptors0. The physical properties, such as chemical potential, chemical hardness, and chemical electrophilicity of all studied molecules, were investigated. Natural population analysis was employed to describe the state of charge transfer between interactions using the natural bond orbital (NBO). The quantum theory atoms in molecules (QTAIM) was used to examine the properties of the bond critical points such as their electron densities and Laplacians. It was found that there were some hydrogen bond interactions between benzoxazepin derivatives and active space PIK3δ. It can be said that the topological parameters derived from the theory of Bader can be applied to estimate the H-bond strength for which the total electron density (H(r)) values at bond critical points(BCPS) are negetive, suggesting that the interactions are hydrogen bonding. Electrophilic charge transfer confirmed that electrons were transferred from the PIK3δ to the benzoxazepin.