Molecular Docking and ADME pharmacokinetic prediction studies of some indole-triazole hydrazone hybrids as anticancer potential via TDO2 inhibition

One of the crucial enzymes in the tryptophan metabolic pathway, tryptophan 2,3-dioxygenase (TDO2), is also a major target for the development of anticancer medications, as it enhances tumor immune evasion mechanisms. Computational studies (in silico) are useful tools for assessing ligand-protein interactions and forecasting binding affinity. To examine the binding pattern of previously described drugs with the TDO2 enzyme's active site, molecular docking was carried out in this work utilizing the PyRx program. Using this technique, the binding energy was predicted, and the important interactions between the ligands and the vital amino acid residues in the active site of the enzyme were examined. The docking results showed that compound 5b has the highest predicted binding affinity toward the target protein, with a binding energy of −8.8 kcal/mol. In addition, an ADME pharmacokinetic property analysis was conducted using SwissADME to predict the pharmacological properties of the studied compounds. According to the findings, most compounds exhibit appropriate physicochemical properties and comply with the Lipinski Rule of Five, indicating potential for oral bioavailability. Overall, the findings of ADME analysis and molecular docking studies suggest that the investigated compounds would be good candidates for additional experimental testing and might aid in the creation of potent TDO2 enzyme inhibitors.