In-silico evaluation of diffractaic acid as novel anti-diabetic inhibitor against dipeptidyl peptidase IV enzyme.

Abstract

Diabetes mellitus (DM) is one of the most common long-term metabolic illnesses with detrimental implications on health and 90-95% of DM cases worldwide are caused by type 2 diabetes (T2DM). The side effects of the existing medicines include vomiting, diarrhea, and serious damage to the kidneys, blood vessels, and nerves. Therefore, finding anti-diabetic medications without side effects is crucial. The main goal of this work is to find anti-diabetic inhibitors using in-silico evaluation techniques such as molecular docking, molecular dynamic simulation, principal component analysis, and drug probability analysis. The DPP-IV is one of numerous molecular targets implicated in the pathogenesis of DM and Diffractaic acid (DF) was docked into the active site of this enzyme to assess the inhibitory effect of DF. In addition, MD simulation and PCA were used to assess the stability of docked complex. Furthermore, the DF was then subjected to drug probability investigations. The binding affinity of the DF was - 40.2476 kcal/mol, which was comparable to the reference compound (- 43.0908 kcal/mol). Furthermore, the compound was in a stable structure, as demonstrated by MD simulation and PCA analysis. Based on drug probability tests, DF also demonstrated druggable qualities. The results of this investigation suggest that DF may function as a possible inhibitor against DM; nevertheless, more in vitro and in vivo investigations are required to validate the activity and other properties.

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00321-9.