<i>In Silico</i> Screening of Phytochemicals Targeting the NF-κB Pathway: A Novel Approach for Pancreatic Cancer Drug Discovery

Pancreatic carcinoma is a common digestive system cancer with a high mortality rate. The NF-[Formula: see text]B pathway plays an important role in promoting inflammation, cell survival and metastasis, which leads to pancreatic cancer progression. In this study, we used different in silico-based drug designing approaches to screen the potential I[Formula: see text]B kinase (IKK) protein inhibitors, a key regulator of the NF-[Formula: see text]B pathway, using bioactive plant-derived compounds. Ten phytochemicals were retrieved from the PubChem database and further used in molecular docking, ADME and toxicity profiling, molecular dynamics (MD) simulations and density functional theory (DFT) calculations to explore the therapeutic potential as IKK inhibitors. This study revealed that Chrysin and Oroxylin A showed high binding energy (−9.3 kcal/mol and −9.0 kcal/mol) compared to the standard drug (−7.8 kcal/mol). Further ADME and toxicity analysis showed that the top compounds have favorable drug-likeness properties and MD analysis showed structural stability of Chrysin and Oroxylin A compounds upon binding to IKK protein compared to the standard drug. MM-PBSA calculations validated the results of molecular docking, which revealed the favorable binding free energies for the top lead compounds. Moreover, DFT calculations showed that Oroxylin A has high structural stability ([Formula: see text] = 0.37491 eV) compared to Chrysin ([Formula: see text] = 0.14874 eV), which indicates its potential as a therapeutic agent. In conclusion, the results of this study suggest that Chrysin and Oroxylin A may serve as promising IKK inhibitors for pancreatic cancer therapy, warranting further in vitro and in vivo validation.