Linalool-based silver nanoconjugates as potential therapeutics for glioblastoma: in silico and in vitro insights
Hina Manzoor, Muhammad Umer Khan, Samiullah Khan, Mohibullah Shah, Chaudhry Ahmed Shabbir, Hamad M. Alkahtani
Abstract
Glioblastoma is the most predominant type of brain tumor, and resistance to medication has hampered the effectiveness of chemotherapy for gliomas. Acyclic monoterpene alcohol, linalool, has a range of pharmacological properties. The present study aimed to evaluate the impact of linalool and its nanoformulation on glioblastoma cell proliferation. DFT and ADMET analyses were used to initially assess the physiochemical characteristics of linalool and the produced silver nanoconjugates, LN@AgNPs. STRING database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to narrow the 6 genes involved in glioblastoma and underwent for molecular docking study. Using AutoDock Vina 1.5.7, ligands were docked to the interaction site of selected targets. Top scored complexes PD-L1/Ligands and PTEN/ligands were simulated using molecular dynamics. The results revealed that LN@AgNPs produced a more stable complex, because metallic bonds are more robust and durable than hydrogen bonds, which give metals their distinctive strength and stability. To confirm the cytotoxicity of the compound against GBM cell line SF-767, linalool and LN@AgNPs were evaluated by in vitro study to check the expression at the IC50 concentration of top scored selected genes. The results indicated that the cytotoxic effects of linalool and LN@AgNPs were concentration dependent. In the SF-767 cancer cell line, linalool and LN@AgNPs with IC50 (33.14 µg/mL and 22.12 µg/mL respectively) values downregulated PD-L1 expression and increased PTEN expression. In conclusion phytocompounds conjugated with AgNPs increased cytotoxicity and inhibition index in glioblastoma cells. Therefore, LN@AgNPs may be a viable option for cancer treatment.