<i>In silico</i> investigation of the interactions, molecular docking, dynamics, and simulation of neoandrographolide against neuroblastoma cancer by targeting wild and mutant ALK

Abstract Neuroblastoma is the most profoundly typical solid tumor in children that is not located in the brain. It affects 7% of all pediatric malignancies. It causes around 15% of all cancer fatalities in children. An important treatment option for treating human neuroblastoma cancer is to block the anaplastic lymphoma kinase (ALK) targets. Current investigations combine molecular docking and dynamic modeling to realistically screen phytochemical inhibitors. The study tested a molecule named neoandrographolide, which is derived from andrographolide, by using molecular docking with ALK protein. We examined the bioavailability of neoandrographolide using the Lipinski rule of five. Molinspiration cheminformatics online software was used to estimate the drug likeliness and the oral bioavailability of neoandrographolide, along with other important physicochemical properties. The toxicity profiles of the compounds have been found utilizing the TOPKAT program within Accelrys Discovery Studio version 3.0, predicated on their molecular structure. The ligand molecule neoandrographolide showed strong attachment in the binding site through several connections, including hydrogen bonds, hydrophobic interactions, also van der Waals interactions, which prevented adenosine triphosphate from binding in both wild ALK (−6.8 kcal/mol) along with mutant ALK (−7.5 kcal/mol). Molecular dynamics simulations revealed that the mutant complex, containing the gatekeeper residue L1196M, exhibits greater structural stability and stronger binding affinity compared to the wild‐type complex, mostly attributable to interactions with the 2H‐furan‐5‐one moiety. The cytotoxicity assay using the SH‐SY5Y cell line revealed an IC 50 value of 75.75 µM, indicating promising anti‐cancer potential based on in vitro results. These results highlight the neoandrographolide hope for a therapeutic agent in the treatment of human neuroblastoma.