Exploring flavonoids for potential inhibitors of a cancer signaling protein PI3Kγ kinase using computational methods

Mohd Rehan; Maged Mostafa Mahmoud; Shams Tabrez; Hani Mutlak A. Hassan; Ghulam M.D. Ashraf

doi:10.21873/anticanres.14460

Exploring flavonoids for potential inhibitors of a cancer signaling protein PI3Kγ kinase using computational methods

Mohd Rehan^*, Maged Mostafa Mahmoud, Shams Tabrez, Hani Mutlak A. Hassan, Ghulam M.D. Ashraf

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	4547-4556
Number of pages	10
Journal	Anticancer Research
Volume	40
Issue number	8
DOIs	https://doi.org/10.21873/anticanres.14460
Publication status	Published - Aug 2020
Externally published	Yes

Keywords

Anti-cancer
Flavonoid
Inhibitor
PI3K
Protein kinase
Virtual screening

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.21873/anticanres.14460

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title = "Exploring flavonoids for potential inhibitors of a cancer signaling protein PI3Kγ kinase using computational methods",

abstract = "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.",

keywords = "Anti-cancer, Flavonoid, Inhibitor, PI3K, Protein kinase, Virtual screening",

author = "Mohd Rehan and Mahmoud, {Maged Mostafa} and Shams Tabrez and Hassan, {Hani Mutlak A.} and Ashraf, {Ghulam M.D.}",

year = "2020",

month = aug,

doi = "10.21873/anticanres.14460",

language = "English",

volume = "40",

pages = "4547--4556",

journal = "Anticancer Research",

issn = "0250-7005",

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T1 - Exploring flavonoids for potential inhibitors of a cancer signaling protein PI3Kγ kinase using computational methods

AU - Rehan, Mohd

AU - Mahmoud, Maged Mostafa

AU - Tabrez, Shams

AU - Hassan, Hani Mutlak A.

AU - Ashraf, Ghulam M.D.

PY - 2020/8

Y1 - 2020/8

N2 - 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.

AB - 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.

KW - Anti-cancer

KW - Flavonoid

KW - Inhibitor

KW - PI3K

KW - Protein kinase

KW - Virtual screening

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SN - 0250-7005

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JO - Anticancer Research

JF - Anticancer Research

IS - 8

ER -

Exploring flavonoids for potential inhibitors of a cancer signaling protein PI3Kγ kinase using computational methods

Abstract

Keywords

UN SDGs

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