DIOSPYROS KAKI’S PHYTOCHEMICAL MEDIATED INHIBITION OF GBM BY TARGETING PDK-1: A MACHINE LEARNING MODEL.

Abstract

Glioblastoma Multiforme (GBM), a grade 4 brain tumour, 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-1 (3-phosphoionsitide-dependent kinase 1) phosphorylation. Targeting and hampering PDK-1 can prevent such activation. Through in-silico analysis, this study seeks to investigate several phytochemicals that have the potential to target PDK-1. 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-1 protein, the results revealed that Diospyrin and Neodiospyrin show maximum binding energies (- 10.6 and -10.4 kcal/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-8I1) compound(-10.1 kcal/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.