Exploring PI3K Isoform Selective Phytochemical Inhibitors: An In Silico Approach

Abstract Abnormal activation of phosphoinositide‐3‐kinase (PI3K) is a common feature of several types of cancer. The development of potential isoform‐selective PI3K inhibitors represents a significant advance in direct targeted therapy. Phytochemical inhibitors may be lesstoxic and safer alternatives for healthy human cells. Therefore, the aim of this study was to investigate plant‐derived potential isoform‐selective phytochemicals. The effects of phytocompounds from the PI3K inhibitor library with low toxicity and drug‐like properties on the PI3K isoform were investigated via in silico analysis. Molecule docking and protein‐ligand flexibility simulations of phytocompounds and PI3K isoforms were performed, and their own drug‐like properties were evaluated via SwissADME. This in silico study revealed that mahanine can inhibit the PI3Kα and PI3Kβ isoforms, whereas morusin can inhibit the PI3Kα isoform, isoangustone A can inhibit the PI3Kβ isoform, hyperoside can inhibit the PI3Kγ isoform, andlavendustin A can inhibit the PI3Kδ isoform. Mahanine, morusin, isoangustone A andlavendustin A have the ability to inhibit PI3K isoforms and can be used in drug development studies after experimental validation.