Finding a Potential Dipeptidyl Peptidase-4 (DPP-4) Inhibitor for Type-2 Diabetes Treatment Based on Molecular Docking, Pharmacophore Generation, and Molecular Dynamics Simulation

Meduru, Harika; Wang, Yeng‐Tseng; Tsai, Jeffrey J. P.; Chen, Yu-Ching

doi:10.3390/ijms17060920

Cited by 38 publications

(25 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To attend this problem, several in silico studies have been carried out to predict which compounds of Ephedra , such as (−)-ephedrine ( 1 ) and five ephedrine derivatives 2 – 6 have potential antidiabetic properties by inhibiting dipeptidyl peptidase IV (DPP-IV). These studies are based on the fact that these compounds are considered oral hypoglycemic agents because they reduce glucagon and blood glucose levels mediated by increasing incretins that are responsible for inhibiting the release of glucagon and for promoting an increase in insulin secretion [ 117 , 118 , 119 ]. Oh et al showed that E. sinica Stapf normalizes hyperglycemia and hyperinsulinemia in obese mice (C57BL/6J), that were fed a high-fat diet [ 120 ].…”

Section: Pharmacological Propertiesmentioning

confidence: 99%

A Review of the Ephedra genus: Distribution, Ecology, Ethnobotany, Phytochemistry and Pharmacological Properties

et al. 2020

View full text Add to dashboard Cite

Ephedra is one of the largest genera of the Ephedraceae family, which is distributed in arid and semiarid regions of the world. In the traditional medicine from several countries some species from the genus are commonly used to treat asthma, cold, flu, chills, fever, headache, nasal congestion, and cough. The chemical constituents of Ephedra species have been of research interest for decades due to their contents of ephedrine-type alkaloids and its pharmacological properties. Other chemical constituents such as phenolic and amino acid derivatives also have resulted attractive and have provided evidence-based supporting of the ethnomedical uses of the Ephedra species. In recent years, research has been expanded to explore the endophytic fungal diversity associated to Ephedra species, as well as, the chemical constituents derived from these fungi and their pharmacological bioprospecting. Two additional aspects that illustrate the chemical diversity of Ephedra genus are the chemotaxonomy approaches and the use of ephedrine-type alkaloids as building blocks in organic synthesis. American Ephedra species, especially those that exist in Mexico, are considered to lack ephedrine type alkaloids. In this sense, the phytochemical study of Mexican Ephedra species is a promising area of research to corroborate their ephedrine-type alkaloids content and, in turn, discover new chemical compounds with potential biological activity. Therefore, the present review represents a key compilation of all the relevant information for the Ephedra genus, in particular the American species, the species distribution, their ecological interactions, its ethnobotany, its phytochemistry and their pharmacological activities and toxicities, in order to promote clear directions for future research.

show abstract

Section: Pharmacological Propertiesmentioning

confidence: 99%

A Review of the Ephedra genus: Distribution, Ecology, Ethnobotany, Phytochemistry and Pharmacological Properties

et al. 2020

View full text Add to dashboard Cite

show abstract

“…CDOCKER is a semi-flexible molecular docking analysis method based on the CHARMm force field, which can produce high-precision docking results, and it provides information on the interaction binding energy and ligand-receptor docking mode [28]. According to the molecular docking results of CDOCKER (Table 3), CDOCKER interactions and binding energies for three of the seven compounds were better than vildagliptin [29]. Therefore, compounds 1-3 may be potential DPP-IV inhibitors based on the above virtual screening and docking processes.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

“…Currently, molecular docking is extensively used for virtual investigation of the interactions between ligands and receptors, which can help to reveal the binding modes and the residues involved in binding interactions. In order to identify potential DPP-IV inhibitors, binding models for interactions between the active sites of DPP-IV, and the inhibitors have been proposed in several investigations [ 18 ]. In the present study, a molecular docking strategy was used to screen the 57 identified peptides and identify DPP-IV inhibitory peptides.…”

Section: Resultsmentioning

confidence: 99%

Rapid Identification of Dipeptidyl Peptidase-IV (DPP-IV) Inhibitory Peptides from Ruditapes philippinarum Hydrolysate

et al. 2017

View full text Add to dashboard Cite

Dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides were rapidly identified from Ruditapes philippinarum hydrolysate. The hydrolysate was fractionated by ethanol precipitation and preparative reverse phase high-performance liquid chromatography (RP-HPLC). The fraction which showed the highest DPP-IV inhibitory activity was then analyzed by a high-throughput nano-liquid chromatography electrospray ionization tandem mass spectrometry (nano-LC ESI-MS/MS) method, and the sequences of peptides were identified based on the MS/MS spectra against the Mollusca protein data from the UniProt database. In total, 50 peptides were identified. Furthermore, molecular docking was used to identify potential DPP-IV inhibitors from the identified peptides. Docking results suggested that four peptides: FAGDDAPR, LAPSTM, FAGDDAPRA, and FLMESH, could bind pockets of DPP-IV through hydrogen bonds, π-π bonds, and charge interactions. The four peptides were chemically synthesized and tested for DPP-IV inhibitory activity. The results showed that they possessed DPP-IV inhibitory activity with IC50 values of 168.72 μM, 140.82 μM, 393.30 μM, and >500 μM, respectively. These results indicate that R. philippinarum-derived peptides may have potential as functional food ingredients for the prevention of diabetes.

show abstract

Finding a Potential Dipeptidyl Peptidase-4 (DPP-4) Inhibitor for Type-2 Diabetes Treatment Based on Molecular Docking, Pharmacophore Generation, and Molecular Dynamics Simulation

Cited by 38 publications

References 36 publications

A Review of the Ephedra genus: Distribution, Ecology, Ethnobotany, Phytochemistry and Pharmacological Properties

A Review of the Ephedra genus: Distribution, Ecology, Ethnobotany, Phytochemistry and Pharmacological Properties

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

Rapid Identification of Dipeptidyl Peptidase-IV (DPP-IV) Inhibitory Peptides from Ruditapes philippinarum Hydrolysate

Contact Info

Product

Resources

About