Diospyros kaki’s phytochemical mediated inhibition of GBM by targeting PDK-1: An in-silico docking and machine learning model.

Glioblastoma Multiforme (GBM), a grade 4 brain tumor, is resistant to standard treatments and exhibits a 100 percent recurrence rate. By obstructing the primary pathways involved in tumour sustenance and progression, GBM can be completely eliminated. Since high levels of p-AKT (Phosphorylated Protein Kinase B) have been detected in recurring GBM, the AKTmTOR pathway has received the most attention in GBM therapies. AKT can be activated by PDK-I (3-phosphoionsitide-dependent kinase1) phosphorylation. Targeting and hampering PDK-I can prevent such activation. Through in-silico analysis, this study seeks to investigate several phytochemicals that have the potential to target PDK-I. The phytochemical profile of Diospyros kaki holds immense significance. Carotenoids, tannins, and phenolic compounds impart Diospyros kaki excellent anti-oxidant potential making it a promising candidate for anticancer drug compound extraction. After docking 40 selected phytochemicals against PDK-I protein, the results revealed that Diospyrin and Neodiospyrin show maximum binding energies (-10.6 and -10.4kcal/mol respectively) comparable to that of the standard inhibitor 2-(5-{[2R)-2-amino-3- phenylpropyloxy}pyridine-3-yl)8,9dimethoxybenzo[c] [2], [7]naphthy ridine-4-amine (ID-SII) compound (-10.1kcal/mol). Validating the docking results by machine learning, multiple analyses were carried out to find the drug likeness, bioactivity and bioavailability of the selected phytochemicals so as to imply them as a therapeutic agent against GBM.