Exploring Flavonoids for Potential Inhibitors of a Cancer Signaling Protein PI3Kγ Kinase Using Computational Methods

• Published in: Anticancer research Vol. 40; no. 8; pp. 4547 - 4556
• Main Authors: REHAN, MOHD, MAHMOUD, MAGED MOSTAFA, TABREZ, SHAMS, HASSAN, HANI MUTLAK A., ASHRAF, GHULAM MD
• Format: Journal Article
• Language: English
• Published: Athens International Institute of Anticancer Research 01.08.2020
• Subjects: 1-Phosphatidylinositol 3-kinase; Anticancer properties; Antitumor activity; Antitumor agents; Binding sites; Bioassays; Cancer; Computer applications; Flavonoids; Inhibitors; Inositol; Kinases; Molecular docking
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.14460

Background/Aim: Phosphatidyl-inositol-3-kinase (PI3K), a cancer therapeutic target, has been exploited for cancer therapy. The natural compounds flavonoids have increasingly been shown to possess anticancer activity. The current study aimed to explore all known flavonoids for their ability to inhibit PI3Kγ. Materials and Methods: Virtual screening of flavonoids using molecular docking to the ATP binding site of PI3Kγ was performed. The top 10 scoring flavonoids were selected for pose analysis and binding strength scores. Results: Molecular docking revealed that the 10 selected flavonoids might inhibit PI3Kγ kinase activity. Literature search did not identify studies reporting a bioassay activity for any of these compounds. Conclusion: All 10 selected flavonoids are potential PI3Kγ kinase inhibitors and anticancer agents. Interestingly, one of the 10 least scoring flavonoids has been reported to be inactive, as expected, and thus validating the accuracy of the results.