| Abstrakt: |
Pancreatic cancer (PC) presents challenges due to limited treatment options and patients seek complementary therapies alongside conventional treatments to improve well-being. This study uses computational drug discovery approaches to find potential phytochemicals from S. singueana for PC treatment. Among the 38 phytochemicals screened from S. singueana, specific inhibitors against PC were selected. Protein–protein interaction (PPI) network analysis highlighted key targets with high degrees, including PTEN (8) and PTK2 (7) genes, along with their respective proteins 5BZX and 3BZ3, which were employed for molecular docking studies. 1-methylchrysene and 3-methyl-1,8,9-anthracenetriol showed strong binding affinities of − 9.2 and − 8.1 Kcal/mol, respectively. Molecular dynamics simulations lasting 300 ns assessed structural stability and interaction energy of compound-target dockings: 1-methylchrysene-PTEN and 3-methyl-1,8,9-anthracenetriol-PTK2. In molecular dynamics simulations, the 3-methyl-1,8,9-anthracenetriol-PTK2 complex showed lower RMSD, RMSF, radius of gyration, solvent-accessible surface area, and more hydrogen bonds than the 1-methylchrysene-PTEN complex. The 3-methyl-1,8,9-anthracenetriol-PTK2 complex exhibited significantly stronger binding with a binding free energy (ΔG) of − 21.92 kcal/mol compared to the less favourable ΔG of − 10.65 kcal/mol for the 1-methylchrysene-PTEN complex. The consistent and stable binding interaction observed in the 3-methyl-1,8,9-anthracenetriol-PTK2 complex highlights its potential as a potent inhibitor of Focal Adhesion Kinase 1. Consequently, it emerges as a promising lead compound for the development of pancreatic cancer therapeutics. Conversely, the fluctuations observed in the 1-methylchrysene-PTEN complex indicate a less stable binding interaction. This indicates the potential of 3-methyl-1,8,9-anthracenetriol as a primary candidate for pancreatic cancer treatment. These findings improve our grasp of S. singueana's multi-target effects and its promise in addressing pancreatic cancer. Nevertheless, additional in-vivo and in-vitro studies are required to validate their effectiveness and therapeutic potential. [ABSTRACT FROM AUTHOR] |
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