Psilostachyin B as Potential Immune Checkpoint Inhibitor Targeting CTLA-4 and PD-L1 in the Development of Cancer Immunotherapy: A Computational Investigation

Immunotherapy is a promising treatment approach by targeting immune checkpoints such as CTLA-4 and PD-L1 to overcome cancer progression. The utilization of Curcuma longa and Phyllanthus niruri as potential immune checkpoint inhibitors offers an alternative cancer therapy. Computational analyses including molecular docking and molecular dynamics with validation using Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA), Dynamic Cross-Correlation Matrix (DCCM), and Principal Component Analysis (PCA), were performed in this study. Results show that Psilostachyin B is the most promising inhibitor candidate against CTLA-4 and PD-L1, with binding affinity values of -6.9 and -6.8 kcal/mol, respectively. Molecular dynamics simulation results indicated that Psilostachyin B exhibited greater stability than the native ligand, with RMSD values remaining below 3 Å for the ligand–complex on CTLA-4 and PD-L1 over 40 ns and 20 ns, respectively. These findings were further supported by favorable binding free energy values from MM-PBSA calculations, as well as positive correlations observed in DCCM and stable conformational profiles revealed by PCA. Moreover, PPI analysis showed that Psilostachyin B interacts with various key cancer-related proteins based on Gene Ontology annotations and KEGG pathway analysis. Psilostachyin B is a promising drug candidate with favorable drug-likeness, high predicted antineoplastic activity (Pa 95%), and efficient membrane permeability. This computational investigation highlights the potential of Psilostachyin B as a novel immune checkpoint inhibitor targeting CTLA-4 and PD-L1, two key regulators involved in modulating the tumor microenvironment and enhancing immune responses. Future studies through in vitro and in vivo studies are necessary to evaluate its efficacy before clinical application.