Potential inhibitors of Dipeptidyl Peptidase IV dependent from Moroccan phytocompound: molecular docking, molecular dynamics simulations, and MM-PBSA analyses

Type 2 Diabetes Mellitus (T2DM) is the most prevalent form of diabetes and is characterized by beta-cell dysfunction and reduced insulin sensitivity. Dipeptidyl peptidase IV (DPP-IV) has emerged as a pivotal target in the development of antihyperglycemic drugs aimed at improving glycemic control. Methods This study aimed to identify potential natural DPP-IV inhibitors through virtual screening of the Moroccan Phytochemical Database (MPDB), using structure-based molecular docking techniques. Phytochemicals were evaluated for their interaction and binding affinity with DPP-IV, and top candidates were selected based on docking scores. Lead compounds were further subjected to molecular dynamics (MD) simulations to examine the stability of their binding within the DPP-IV active site, alongside silico Absorption, Distribution, Metabolism, and Excretion (ADME) analyses to assess their pharmacokinetic profiles. Results The findings revealed that Quercitrin and Hesperidin showed greater affinity and stability in interactions with the target enzyme DPP-IV compared to the reference compound Sitagliptin. ADME calculations showed that such phytocompounds showed good pharmacokinetic properties. MD simulations for 150 ns validated that Quercitrin and Hesperidin showed sustained stability and good binding energy in the active site of the target enzyme compared to Sitagliptin. Conclusion Overall, quercitrin and hesperidin, isolated from Moroccan plants Argania spinosa and Anabasis aretioides, respectively, translate into potential natural DPP-IV inhibitors with antihyperglycemic activities. Their potential therapeutic application towards the control of postprandial blood glucose in the case of individuals suffering from T2DM is reinforced, and the compounds represent a natural option whose pharmacokinetic profile is acceptable.