Unravelling the potential of Diospyros species in the treatment of pancreatic adenocarcinoma using an in-silico approach

Pancreatic cancer remains one of the fatal malignancies with limited treatment options and a high rate of drug resistance. Y-box binding protein 1 (YBX1) plays an essential role in pancreatic cancer by upregulating the low- density lipoprotein receptor-related protein-1 (LRP1), which promotes tumour growth through the Wnt/?- catenin pathway. Diospyros genus exhibits anticancer properties and could be used to overcome drug resistance and inhibit pancreatic ductal adenocarcinoma (PDAC). The Cancer Genome Atlas (TCGA) data and TNMplot were analyzed to perform bioinformatics analyses to investigate LRP1 gene alterations and their correlation with YBX1 in PDAC. Diospyros phytochemicals with high binding affinities for YBX1 (PDB ID: 6KTC) were screened through molecular docking. Further, these phytochemicals' pharmacokinetics, drug likeness and toxicity were evaluated using ADMETlab 2.0 and ProTox 3.0. According to bioinformatics analysis, the expression of YBX1 and LRP1 in PDAC samples were significantly correlated. Molecular docking identified 13 phytochemicals with high binding affinities (? -7.5 kcal/mol) for YBX1.Diospyrin (-9.1 kcal/mol), Kaempferol (-7.5 kcal/mol), Mamegakinone (-9.1 kcal/mol) and Neodiospyrin (-8.6 kcal/mol) showed favourable interactions. ADMET analysis confirmed that these four compounds exhibited drug-like properties. Diosprin and Kaempferol have established anticancer effects by inducing apoptosis and inhibiting carcinogenic pathways; however, Mamegakinone and Neodiospyrins’ roles need further investigation using experimental studies. The promising binding affinities of these compounds suggest potential therapeutic applications in PDAC. This study highlights the potential of phytochemicals in the genus Diospyros as potential therapeutic molecules against YBX1 in PDAC.