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

AuthorMaryam Bayanatien
AuthorMohammad Ismail Mahboubi Rabbanien
AuthorShirin Sirous Kabirien
AuthorBahareh Miren
AuthorElham Rezaeeen
AuthorSayyed Abbas Tabatabaien
OrcidMaryam Bayanati [0000-0002-1225-7538]en
OrcidElham Rezaee [0000-0002-6458-0097]en
OrcidSayyed Abbas Tabatabai [0000-0002-7363-3517]en
Issued Date2024-12-31en
AbstractContext: Dipeptidyl peptidase 4 (DPP-4) is a serine exopeptidase enzyme that hydrolyzes the amide bond at the N-terminal of peptides. This enzyme converts incretins, such as glucagon-like peptide I and glucose-dependent insulinotropic peptide, into their inactive forms, thereby preventing them from stimulating insulin secretion. Numerous studies have confirmed the role of DPP-4 in the pathophysiology of type 2 diabetes, leading to the development of various DPP-4 inhibitors. In recent years, research on DPP-4 inhibitors has expanded significantly, resulting in the creation of both non-peptidomimetic heterocyclic compounds and peptidomimetic scaffolds. Evidence Acquisition: This systematic review summarizes all recent advances related to DPP-4 inhibitors up to 2024. It begins by outlining the biochemical characteristics of DPP-4 and general pharmacological principles of DPP-4 inhibition, followed by an overview of the latest developments from recent publications. The review provides valuable insights into the pharmacophores necessary for ligand-protein interactions, aimed at understanding the structure-activity relationship of novel DPP-4 inhibitors. Data for this review was collected from sources including ScienceDirect, PubMed, and Scopus. Results: This review highlights various chemical scaffolds that have been explored in the development of novel DPP-4 inhibitors. It emphasizes scaffolds with significant DPP-4 inhibitory activity, including azoles, azines, sulfonamides, and quinolone motifs. The article also details the structure-activity relationships of newly developed analogs, providing a comprehensive overview of recent advancements in this area. Conclusions: Despite moderate progress in the development of novel DPP-4 inhibitors, emerging molecular aspects of DPP-4 intervention show great promise for future therapeutic developments.en
DOIhttps://doi.org/10.5812/ijpr-151581en
KeywordDPP-4 Inhibitorsen
KeywordDipeptidyl Peptidase-4en
KeywordDockingen
PublisherBrieflandsen
TitleDipeptidyl Peptidase-4 Inhibitors: A Systematic Review of Structure-Activity Relationship Studiesen
TypeReview Articleen

Files