Molecular Docking of Natural Compounds as DPP-4 Inhibitors in Type 2 Diabetes: A Comprehensive Review

Area of Science:

• Pharmacology
• Computational Chemistry
• Natural Products Chemistry

Background:

• Dipeptidyl peptidase-4 (DPP-4) is a key target for type 2 diabetes mellitus (T2DM) treatment, regulating glucose homeostasis.
• Existing DPP-4 inhibitors show moderate efficacy, prompting research into novel compounds from natural sources.
• Molecular docking is a vital computational tool for discovering potential DPP-4 inhibitors.

Purpose of the Study:

• To critically review and analyze molecular docking studies of natural compounds targeting DPP-4.
• To evaluate the methodologies, protein structures, and validation strategies employed in these studies.
• To identify trends and limitations in the computational identification of natural DPP-4 inhibitors.

Main Methods:

• Systematic literature search and evaluation of over 150 molecular docking studies.
• Analysis of docking protocols, protein structures (e.g., 1X70, 6B1E), and validation approaches.
• Categorization of natural compounds investigated, focusing on flavonoids, alkaloids, phenolics, terpenoids, and peptides.

Main Results:

• Significant variability exists in computational protocols across studies.
• Flavonoids are the most studied class of natural compounds targeting DPP-4.
• Many studies report favorable binding but lack experimental validation or advanced computational analysis like molecular dynamics.

Conclusions:

• Molecular docking offers valuable preliminary insights into natural DPP-4 inhibitors.
• There is a critical need for improved standardization of computational methods.
• Integration with experimental assays and molecular dynamics is essential for reliable and translatable findings.