In-silico screening of anti-cancer natural compounds targeting NF-κB as identification of potential therapeutic inhibitor.

In the modern world, cancer is now one of the most significant causes of death. Nuclear factor-kappa B (NF-κB) is critical for inflammation and immune responses. Still, its abnormal activation or dysfunction can promote tumor cell proliferation and inhibit apoptosis, thereby initiating cancer progression. The objectives of this study are to discover the potential lead molecules with anti-cancer activity against NF-κB complexed with DNA (PDB ID: 1A3Q) through virtual screening based on the NPACT and containing 1574 anti-cancer natural compounds. All compounds were docked against 1A3Q using PyRx, and the first three molecules from the docking results were selected for further ADMET analysis using ADMETlab3.0 and Protox 3.0. The top three natural compounds were stable against NF-κB, had high GI absorption and low toxicity, and exhibited high binding affinities. One of these molecules (PubChem ID: 21600009) is drug-like for cancer, with a binding affinity of - 8.7 kcal/mol, which is why it was considered more significant than the other two compounds. Then, the best compound obtained from those calculations was included in GROMACS 2022.4 to evaluate its dynamic properties and interactions with the receptor. A simulation was carried out using the CHARMM36 force field and TIP3P water model. The electronic properties of the compound have also been calculated to confirm its drug-likeness using DFT at the B3LYP/6-31G(d,p) level in Gaussian 09. These comparative studies therefore indicate the potential of a cancer drug candidate that requires further experimental testing to verify its stability and biological efficacy.