Atta Ullah, Saeed Ullah, Muhammad Waqas, Majid Khan, Najeeb Ur Rehman, Asaad Khalid, Afnan Jan, Shahkar Aziz, Muhammad Naeem, Sobia Halim, Ajmal Khan* and Ahmed Al-Harrasi Pages 1 - 18 ( 18 )
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.
Method: 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, andQTME-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.
Glioblastoma, EGFR, PI3K, molecular docking, virtual screening, MTT assay, U87 cell line.