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.
background:
NA
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.