Dipeptidyl Peptidase-4 Inhibitors: A Systematic Review of Structure-Activity Relationship Studies

Area of Science:

• Biochemistry and Pharmacology
• Medicinal Chemistry

Background:

• Dipeptidyl peptidase 4 (DPP-4) is a key enzyme in glucose metabolism, inactivating incretins and contributing to type 2 diabetes pathophysiology.
• Numerous DPP-4 inhibitors have been developed, targeting this enzyme to improve insulin secretion and glycemic control.

Purpose of the Study:

• To provide a comprehensive systematic review of recent advances in DPP-4 inhibitors up to 2024.
• To elucidate the biochemical characteristics of DPP-4 and pharmacological principles of its inhibition.
• To explore novel chemical scaffolds and their structure-activity relationships (SAR) for DPP-4 inhibitor development.

Main Methods:

• Systematic literature review of recent publications up to 2024.
• Data collection from major scientific databases: ScienceDirect, PubMed, and Scopus.
• Analysis of chemical scaffolds and SAR for DPP-4 inhibitory activity.

Main Results:

• Identified key chemical scaffolds with significant DPP-4 inhibitory activity, including azoles, azines, sulfonamides, and quinolone motifs.
• Detailed the SAR of newly developed DPP-4 inhibitor analogs.
• Highlighted the importance of specific pharmacophores for ligand-protein interactions.

Conclusions:

• Recent research has expanded the diversity of DPP-4 inhibitor scaffolds beyond traditional designs.
• Emerging molecular insights into DPP-4 intervention offer promising avenues for future therapeutic strategies.
• Continued exploration of novel DPP-4 inhibitors holds potential for improved type 2 diabetes management.