Identification of Potential Dipeptidyl Peptidase (DPP)-IV Inhibitors among Moringa oleifera Phytochemicals by Virtual Screening, Molecular Docking Analysis, ADME/T-Based Prediction, and In Vitro Analyses

Abstract

Moringa oleifera Lam. (MO) is called the “Miracle Tree” because of its extensive pharmacological activity. In addition to being an important food, it has also been used for a long time in traditional medicine in Asia for the treatment of chronic diseases such as diabetes and obesity. In this study, by constructing a library of MO phytochemical structures and using Discovery Studio software, compounds were subjected to virtual screening and molecular docking experiments related to their inhibition of dipeptidyl peptidase (DPP-IV), an important target for the treatment of type 2 diabetes. After the four-step screening process, involving screening for drug-like compounds, predicting the absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of pharmacokinetic properties, LibDock heatmap matching analysis, and CDOCKER molecular docking analysis, three MO components that were candidate DPP-IV inhibitors were identified and their docking modes were analyzed. In vitro activity verification showed that all three MO components had certain DPP-IV inhibitory activities, of which O-Ethyl-4-[(α-l-rhamnosyloxy)-benzyl] carbamate (compound 1) had the highest activity (half-maximal inhibitory concentration [IC50] = 798 nM). This study provides a reference for exploring the molecular mechanisms underlying the anti-diabetic activity of MO. The obtained DPP-IV inhibitors could be used for structural optimization and in-depth in vivo evaluation.

“Fei Yan No. 1” as a Combined Treatment for COVID-19: An Efficacy and Potential Mechanistic Study

“…A total of 1643 components were obtained. Since antiviral components are absorbed via oral administration, the screening process for bioactive ingredients should include an assessment of drug-likeness (DL) and oral bioavailability (OB) ( Yang et al, 2020b ). The OB and DL of all compounds within QFDYG were extracted from the TCMSP database, finding that 122 compounds met the specified requirements.…”

Compound Prunetin Induces Cell Death in Gastric Cancer Cell with Potent Anti-Proliferative Properties: In Vitro Assay, Molecular Docking, Dynamics, and ADMET Studies

“…The emphasis of a modeling approach with drug-likeness prediction provides potential merits in the application of drug discovery [ 17 ]. With the use of structure-based screening of drug molecules by ADMET prediction tools, the properties of candidates can be evaluated in terms of human intestinal absorption (HIA), blood–brain barrier (BBB) penetration, inhibition of cytochrome P450 2D6, plasma protein binding, aqueous solubility, and toxicity [ 18 ]. This aids in the exclusion of lead compounds that have low drug ability which reduces the cost and improves the efficacy of the drug in the development of pharmaceuticals [ 19 ].…”

Release of dipeptidyl peptidase IV inhibitory peptides from salmon (Salmosalar) skin collagen based on digestion–intestinal absorption invitro

“…DPP-IV activity was measured as described by Yang et al with minor modifications (Yang et al, 2020). Human recombinant DPP-IV enzyme, assay substrate (Gly-Pro-AMC) and assay buffer were included in the DPP-IV inhibitor screening assay kit (Abnova, Taipei, Taiwan).…”