Immunotherapy using checkpoint inhibitors blocks the checkpoint proteins (programmed cell death receptor-1; PD-1) from binding with their corresponding ligands (programmed cell death receptor ligand-1; PD-L1) to regulate cell signaling pathways. The marine environment holds a huge source of small molecules that are understudied which can be developed as an inhibitor. Hence, this study investigated the inhibitory effect of 19 algae-derived small molecules against PD-L1 by using molecular docking, absorption, distribution, metabolism, and elimination (ADME) properties and molecular dynamics simulations (MDS). The molecular docking revealed that the binding energy of the six best compounds ranges from -11.1 to -9.1 kcal/mol. Fucoxanthinol, in particular, has the strongest binding energy at -11.1 kcal/mol with three hydrogen bonds (ASN:63A, GLN:66A, and ASP:122A). Meanwhile, the MDS demonstrated that the ligands were strongly bound to the protein, indicating the stability of the complexes. In summary, the identified compounds are potential PD-L1 inhibitors in immunotherapy.Communicated by Ramaswamy H. Sarma.
Keywords: anti-cancer; bioactive conpounds; immunotherapy; molecular docking; programmed cell death; programmed cell death ligand.