Drug Design: Indole Derivatives as Indoleamine 2,3-Dioxygenase-1 Enzyme Inhibition Using In Silico Approach

Computational studies were used to predict molecular interactions between active compounds and biological targets.This approach helps the pharmaceutical and food industries accelerate the drug discovery process and reduce the costs and risks of failure in clinical trials.A combination of computational chemistry techniques has been carried out, such as quantum mechanical modeling, molecular docking, quantitative structure-activity relationship-2 dimension (QSAR-2D), molecular dynamics simulations, and pharmacokinetic predictions to carry out drug designs for indole derivatives.The purpose of this study was to find indole candidates that have the potential to inhibit the indoleamine 2,3-dioxygenase-1 (IDO1) enzyme, which is responsible for the development of cancer cells.The QSAR-2D equation model shows better predictive strength through internal and external validations.Moreover, the screening results show that the proposed compounds 78 and 79 were selected by meeting the criteria for the candidate with the lowest grid score and predicted IC50.Molecular dynamics simulation was performed to refine the affinity energy calculations of the ligand-receptor.The results show free energy binding (Gbind) candidate (kcal/mol) < Gbind reference (native ligand/XNL: -28.97 0.25, C78: -32.88 0.33, and C79: -35.31 0.35).Furthermore, the pharmacokinetic properties of C78 and C79, such as drug-likeness,