Bioactive compounds derived from marine source: a potential immunotherapy treatment

Abstract

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:

• molecular docking
• programmed cell death
• programmed cell death ligand
• anti-cancer
• immunotherapy
• bioactive conpounds
  

Authors’ Contributions

Conceptualization and supervision, L.P.W.G., J.A.G. and M.S.S.; methodology, formal analysis, data curation, visualization, Y.J. and N.Y. writing—original draft preparation, Y.J., N.Y. and L.P.W.G.; writing—review and editing, Y.J., N.Y., M.S.S., J.A.G. and L.P.W.G. Funding, M.S.S. All authors have read and agreed to the published version of the manuscript.

Disclosure Statement

The authors declare no conflict of interest.

Data Availability Statement

Data are available upon request from the corresponding author.

Additional information

Funding

This study is supported by Universiti Malaysia Sabah Grant (DN20088).