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
:1. Introduction
2. Results and Discussion
3. Materials and Methods
3.1. Literature Search and Establishment of Ligand Library
3.2. First-Round Screening Using Lipinski’s “Rule of Five”
3.3. Second-Round Screening on the Basis of ADME/T Properties
3.4. Third-Round Screening Using LibDock
3.5. Fourth-Round Screening Using CDOCKER Molecular Docking Analysis and Docking Mode Analysis
3.6. In Vitro DPP-IV Inhibition Assay
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds 1, 2 and 3 are available from the authors. |
Compound Number | Absorption Level a | BBB Level b | CYP2D6 Inhibition | Plasma Protein Binding | Solubility Level c |
---|---|---|---|---|---|
1 | 0 | 4 | No | Weak | 4 |
2 | 0 | 3 | No | Weak | 4 |
3 | 0 | 2 | No | Weak | 2 |
4 | 0 | 4 | No | Weak | 4 |
5 | 0 | 4 | No | Weak | 4 |
6 | 0 | 3 | No | Weak | 3 |
7 | 0 | 3 | No | Weak | 4 |
8 | 0 | 4 | No | Weak | 4 |
9 | 0 | 2 | No | Weak | 4 |
10 | 0 | 2 | No | Weak | 4 |
11 | 0 | 3 | No | Weak | 3 |
12 | 0 | 4 | No | Weak | 3 |
13 | 0 | 3 | No | Weak | 3 |
14 | 0 | 3 | No | Weak | 4 |
15 | 0 | 3 | No | No | 4 |
16 | 0 | 3 | No | No | 4 |
17 | 0 | 3 | No | No | 4 |
18 | 0 | 3 | No | No | 4 |
19 | 0 | 3 | No | No | 4 |
20 | 1 | 4 | No | No | 4 |
21 | 0 | 2 | No | No | 4 |
22 | 0 | 3 | No | No | 3 |
23 | 0 | 3 | No | No | 4 |
Compound Number | LibDock Score |
---|---|
3 | data |
5 | 120.126 |
1 | 110.991 |
6 | 109.801 |
4 | 103.673 |
7 | 102.232 |
2 | 99.719 |
Vildagliptin | 93.424 |
Compound Number | CDOCKER Interaction Energy (kcal/mol) | Binding Energy (kcal/mol) | Number of Hydrogen Bonds | Number of Hydrophilic Bonds |
---|---|---|---|---|
1 | 44.9575 | −84.9987 | 4 | 4 |
2 | 39.3594 | −81.1002 | 6 | 1 |
3 | 35.7187 | −47.3644 | 1 | 4 |
Vildagliptin | 35.6244 | −42.0109 | 4 | 3 |
Compound | 1 | 2 | 3 | Vildagliptin |
---|---|---|---|---|
Molecular weight | 341.36 | 311.35 | 377.39 | 303.40 |
H-bond acceptor | 8 | 6 | 8 | 5 |
H-bond donor | 4 | 3 | 4 | 2 |
No. of ionization states | 1 | 1 | 1 | 3 |
No. of tautomers | 1 | 1 | 1 | 1 |
Aerobic biodegradability | Degradable | Nondegradable | Degradable | Degradable |
Ames mutagenicity | Nonmutagen | Nonmutagen | Nonmutagen | Nonmutagen |
Mouse NTP classification a | Noncarcinogen | Noncarcinogen | Noncarcinogen | Noncarcinogen |
Rat NTP classification a | Noncarcinogen | Noncarcinogen | Noncarcinogen | Noncarcinogen |
WOE prediction | Noncarcinogen | Noncarcinogen | Noncarcinogen | Noncarcinogen |
Hepatotoxicity | Yes | Yes | No | No |
Skin sensitization | Mild | Mild | Mild | Mild |
TD50 (mg/kg) | 32.81 | 19.78 | 5.14 | 1.48 |
LC50 (g/L) | 0.58 | 0.15 | 0.05 | 0.26 |
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Yang, Y.; Shi, C.-Y.; Xie, J.; Dai, J.-H.; He, S.-L.; Tian, Y. 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. Molecules 2020, 25, 189. https://doi.org/10.3390/molecules25010189
Yang Y, Shi C-Y, Xie J, Dai J-H, He S-L, Tian Y. 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. Molecules. 2020; 25(1):189. https://doi.org/10.3390/molecules25010189
Chicago/Turabian StyleYang, Yang, Chong-Yin Shi, Jing Xie, Jia-He Dai, Shui-Lian He, and Yang Tian. 2020. "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" Molecules 25, no. 1: 189. https://doi.org/10.3390/molecules25010189