Citronellol silver nanoconjugates as a therapeutic strategy for glioblastoma through computational and experimental evaluation

Glioblastoma is the most prevalent type of brain tumor, and because of drug resistance, treatment for gliomas has been less successful. Citronellol is an acyclic monoterpene alcohol with various pharmacological properties. This study aimed to evaluate the effect of citronellol and its nanoformulation on glioblastoma cell proliferation. The physicochemical properties of citronellol and its synthesized silver nanoconjugates (CN@AgNPs) were evaluated using DFT and ADMET studies. The targets of the investigation (p53 and CDK4) were identified through the application of chemogenomics and analysis of the STRING protein-protein interaction network. Ligands were docked to the interaction sites of specific targets using AutoDock Vina 1.5.7. Molecular dynamics were used to mimic the citronellol complex CDK4 and p53. Because metallic bonds, which provide metals with unique strength and stability, are more resilient and long-lasting than hydrogen bonds, the results showed that the CN@AgNPs generated a more stable complex. Citronellol and CN@AgNPs were assessed by an in vitro study to determine the expression of IC50 concentration for the top scored selected genes to confirm the cytotoxicity of the compound against the GBM cell line SF-767. The findings showed that Citronellol and CN@AgNPs had concentration-dependent cytotoxic effects. Citronellol and CN@AgNPs, with IC50 values of 20.04 ± 4 µg/mL and 19.67 ± 4 µg/mL, respectively, decreased CDK4 expression and raised p53 expression in the SF-767 cancer cell line. In conclusion, the cytotoxicity and inhibition index of glioblastoma cells were increased by the phytocompounds coupled with AgNPs. Therefore, CN@AgNPs may be a good choice for treating cancer.