Novel Natural Inhibitors for Glioblastoma by Targeting Epidermal Growth Factor Receptor and Phosphoinositide 3-kinase


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Abstract

Background/Aim:Glioblastoma is an extensively malignant neoplasm of the brain that predominantly impacts the human population. To address the challenge of glioblastoma, herein, we have searched for new drug-like candidates by extensive computational and biochemical investigations.

Methods:Approximately 950 compounds were virtually screened against the two most promising targets of glioblastoma, i.e., epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K). Based on highly negative docking scores, excellent binding capabilities and good pharmacokinetic properties, eight and seven compounds were selected for EGFR and PI3K, respectively.

Results:Among those hits, four natural products (SBEH-40, QUER, QTME-12, and HCFR) exerted dual inhibitory effects on EGFR and PI3K in our in-silico analysis; therefore, their capacity to suppress the cell proliferation was assessed in U87 cell line (type of glioma cell line). The compounds SBEH-40, QUER, and QTME-12 exhibited significant anti-proliferative capability with IC50 values of 11.97 ± 0.73 µM, 28.27 ± 1.52 µM, and 22.93 ± 1.63 µM respectively, while HCFR displayed weak inhibitory potency (IC50 = 74.97 ± 2.30 µM).

Conclusion:This study has identified novel natural products that inhibit the progression of glioblastoma; however, further examinations of these molecules are required in animal and tissue models to better understand their downstream targeting mechanisms.

About the authors

Atta Ullah

Natural and Medical Sciences Research Center, University of Nizwa

Email: info@benthamscience.net

Saeed Ullah

Natural and Medical Sciences Research Center, University of Nizwa

Email: info@benthamscience.net

Muhammad Waqas

Natural and Medical Sciences Research Center, University of Nizwa

Email: info@benthamscience.net

Majid Khan

Natural and Medical Sciences Research Center, University of Nizwa

Email: info@benthamscience.net

Najeeb Rehman

Natural and Medical Sciences Research Center, University of Nizwa

Email: info@benthamscience.net

Asaad Khalid

Substance Abuse and Toxicology Research Center, Jazan University

Email: info@benthamscience.net

Afnan Jan

Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University

Email: info@benthamscience.net

Shahkaar Aziz

Institute of Biotechnology and Genetic Engineering, The University of Agriculture

Email: info@benthamscience.net

Muhammad Naeem

College of Life Science, Hebei Normal University

Email: info@benthamscience.net

Sobia Halim

Natural and Medical Sciences Research Center, University of Nizwa

Author for correspondence.
Email: info@benthamscience.net

Ajmal Khan

Natural and Medical Sciences Research Center, University of Nizwa

Author for correspondence.
Email: info@benthamscience.net

Ahmed Al-Harrasi

Natural and Medical Sciences Research Center, University of Nizwa

Author for correspondence.
Email: info@benthamscience.net

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