Docking Studies, Synthesis and Evaluation of Novel Pyrimidin-2-one Derivatives As a Dipeptidyl Peptidase IV Inhibitors

Diabetes is a disorder which is characterized by increase in blood glucose level beyond normal value. Now days it is a metabolic disorder and considered as one of the major cause for the death of patients worldwide. Hence there is always a need for the development of newer scaffolds which are useful in treatment of diabetes. In the research computational chemistry plays an important role to discover new possible medicines. In this work, docking analysis has been carried out to study the effects of substituted pyrimidin-2-one on Dipeptidyl peptidase-4 (DPP4). Docking study shows that compound A5 having 2,4-difluorophenyl and 2-hydroxy phenyl group has a potent (IC50 28.13 µM), selective and in vitro efficacious DPP-4 inhibitor. Further molecular modeling revealed compound A5 can fit in the enzyme pocket topologically very well with the pyrimidin-2-one moiety providing hydrogen bond interaction with Glu 205 and Ser 209 of DPP-4. Based on these results, compound A5 might be a promising lead compound for further optimization in the treatment of T2DM.

A high-throughput screening assay for dipeptidyl peptidase-IV inhibitors using human plasma

Dipeptidyl peptidase-IV (DPP-IV) plays a critical role in glucose metabolism and has become an important target for type 2 diabetes mellitus. We previously reported a two-photon fluorescence probe glycyl-prolyl-N-butyl-4-amino-1,8-naphthalimide (GP-BAN)...

Dipeptidyl Peptidase IV Inhibitors for Nonalcoholic Fatty Liver Disease – Systematic Review and Metanalysis

Introduction:: Hepatic steatosis is a frequent condition, that afflicts, especially, obese and insulin resistant patients; diagnosis is made, usually, through imaging tests. Despite the high prevalence and risk of complications, there is no specific treatment approved, though a vast number of medications have been tested. Objective:: To determine the efficacy of dipeptidyl peptidase IV inhibitors (i DPP-IV) in the treatment of NAFLD. Methods:: We searched the electronic databases of the Cochrane Library, MEDLINE, EMBASE and LILACS, as well as reference lists of the included studies and grey literature; 9 studies were selected for inclusion. Results:: 7 studies were used for metanalysis, for 3 outcomes. i DPP-IV showed an ALT-reducing power of MD -10.83 [95% CI 35.23 to 13.57] at 3 months and MD -9.27 [95% CI 10.92 to -7.62] at 6 months of intervention, as well as reduction of hepatic steatosis via MRI of SMD 0.10 [95% CI 0.31 to 0.50]; the overall incidence of adverse events was very low. The studies were considered of low and very low quality by the GRADE evaluation. Conclusion:: Because of the poor overall quality of the studies and heterogeneity of the population analyzed, i DPP-IV did not show efficacy on inflammatory markers or fibrosis in patients with NAFLD.