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 akey role in a variety of immune-mediated disorders such as asthma, rheumatoid arthritis andother inflammatory disease [1]. Inhibitor is a substance that decreases the rate or stops completelya 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 densityfunctional theory (DFT) method. DFT calculations at the B3lyp/6-31G* level were performed toinvestigate the interaction properties and molecular descriptors0. The physical properties, such aschemical potential, chemical hardness, and chemical electrophilicity of all studied molecules,were investigated. Natural population analysis was employed to describe the state of chargetransfer between interactions using the natural bond orbital (NBO). The quantum theory atoms inmolecules (QTAIM) was used to examine the properties of the bond critical points such as theirelectron densities and Laplacians. It was found that there were some hydrogen bond interactionsbetween benzoxazepin derivatives and active space PIK3δ. It can be said that the topologicalparameters derived from the theory of Bader can be applied to estimate the H-bond strength forwhich the total electron density (H(r)) values at bond critical points(BCPS) are negetive,suggesting that the interactions are hydrogen bonding. Electrophilic charge transfer confirmedthat electrons were transferred from the PIK3δ to the benzoxazepin.

Keywords:

Inhibitor , Density Functional Theory , Phosphoinositide-3-Kinase Delta