A Molecular Modeling Investigation of the Therapeutic Potential of Marine Compounds as DPP-4 Inhibitors

Mar Drugs. 2022 Dec 13;20(12):777. doi: 10.3390/md20120777.


Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by elevated levels of blood glucose due to insulin resistance or insulin-secretion defects. The development of diabetes is mainly attributed to the interaction of several complex pathogenic, genetic, environmental and metabolic processes. Dipeptidyl peptidase-4 (DPP-4) is a serine protease that cleaves X-proline dipeptides from the N-terminus of several polypeptides, including natural hypoglycemic incretin hormones. Inhibition of this enzyme restores and maintains glucose homeostasis, making it an attractive drug target for the management of T2DM. Natural products are important sources of bioactive agents for anti-T2DM drug discovery. Marine ecosystems are a rich source of bioactive products and have inspired the development of drugs for various human disorders, including diabetes. Here, structure-based virtual screening and molecular docking were performed to identify antidiabetic compounds from the Comprehensive Marine Natural Products Database (CMNPD). The binding characteristics of two shortlisted compounds, CMNPD13046 and CMNPD17868, were assessed using molecular dynamics simulations. Thus, this study provides insights into the potential antidiabetic activity and the underlying molecular mechanism of two compounds of marine origin. These compounds could be investigated further for the development of potent DPP-4 inhibitors.

Keywords: DPP-4; diabetes; marine compounds; molecular docking; molecular dynamics.

MeSH terms

  • Biological Products* / chemistry
  • Biological Products* / pharmacology
  • Databases, Pharmaceutical*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Dipeptidyl-Peptidase IV Inhibitors* / chemistry
  • Dipeptidyl-Peptidase IV Inhibitors* / pharmacology
  • Drug Evaluation, Preclinical
  • Ecosystem
  • Humans
  • Hypoglycemic Agents* / chemistry
  • Hypoglycemic Agents* / pharmacology
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Structure-Activity Relationship


  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Biological Products