Isolation of Antidiabetic Withanolides from Withania coagulans Dunal and Their In Vitro and In Silico Validation
Abstract
:1. Introduction
2. Experimental
2.1. General Experimental Method
2.2. Plant Material
2.3. Extraction and Isolation
2.4. Acidic Hydrolysis of Compound 1
2.5. In Vitro α-Glucosidase Inhibition Assay
2.6. In Vitro Antiglycation Assay
2.7. Software Used/Statistical Analysis
2.8. Homology Modeling and Molecular Docking
2.9. Molecular Dynamics Simulation and Binding Free Energy Calculations
3. Results and Discussion
3.1. Characterization of the Isolated Compounds
3.2. Biological Activity
3.3. Molecular Modeling and Simulations
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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C. No. | δC | δH (J, Hz) | C. No. | δC | δH (J, Hz) |
---|---|---|---|---|---|
1 | 220.4 | - | 18 | 20.7 | 1.35 s |
2 | 40.5 | 2.31, 2.12 | 19 | 18.2 | 1.27 s |
3 | 75.0 | 3.84 br m, (W1/2 = 14.5) | 20 | 78.1 | - |
4 | 41.0 | 2.04, 2.01 m | 21 | 21.1 | 1.59 |
5 | 136.3 | - | 22 | 83.1 | 4.23 dd (13.2, 3.4) |
6 | 123.6 | 4.58 br s | 23 | 32.9 | 1.60, 1.84 overlap |
7 | 32.6 | 1.77, 1.75 m | 24 | 160.1 | - |
8 | 22.1 | 1.63 m | 25 | 126.4 | - |
9 | 21.0 | 1.61 m | 26 | 168.0 | - |
10 | 52.7 | - | 27 | 62.7 | 4.30 d (11.4), 4.31 d (11.7) |
11 | 21.1 | 1.27, 1.35 m | 28 | 18.0 | 2.01 s |
12 | 20.8 | 1.61, 2.01 m | 1′ | 104.0 | 4.36 d (7.6) |
13 | 49.0 | - | 2′ | 75.0 | 3.31 t (8.1) |
14 | 85.5 | - | 3′ | 74.0 | 3.65 overlap |
15 | 22.3 | 1.63, 1.75 m | 4′ | 71.6 | 3.33 overlap |
16 | 32.8 | 1.35, 1.09 m | 5′ | 78.0 | 3.33 overlap |
17 | 50.5 | 2.30 t (9.4) | 6′ | 63.5 | 3.64 dd (11.8, 4.8), 3.84 d (11.8) |
Compound | α-Glucosidase Inhibition | Antiglycation |
---|---|---|
IC50 (µM) ± (SEM) | IC50 (µM) ± (SEM) | |
1 | Inactive | Inactive |
2 | 683 ± 0.94 | Inactive |
3 | Inactive | Inactive |
4 | 407 ± 4.5 | Inactive |
5 | 66.7 ± 3.6 | Inactive |
6 | Inactive | Inactive |
Standard | 440.99 ± 0.01 a | 288.9 ± 1.84 b |
Template (S. cerevisiae Isomaltase) | Model (S. cerevisiae α-Glucosidase) |
---|---|
Catalytic residues | |
Asp215 | Asp214 |
Glu277 | Glu276 |
Asp352 | Asp349 |
Extended active site residues | |
Asp69 | Asp68 |
Tyr72 | Tyr71 |
Val109 | Val108 |
His112 | His111 |
Tyr158 | Phe157 |
Phe159 | Phe158 |
Phe178 | Phe177 |
Gln182 | Gln181 |
Arg213 | Arg212 |
Val216 | Thr215 |
Gln279 | Ala278 |
Phe303 | Phe300 |
Arg315 | Arg312 |
His351 | His348 |
Gln353 | Gln350 |
Glu411 | Asp408 |
Arg442 | Arg439 |
Arg446 | Arg443 |
Interacting water molecules | |
1021, 1026, 1056, 1058, 1061, 1087, 1102, 1122, 1174, 1228 | 1021, 1026, 1056, 1058, 1061, 1087, 1102, 1122, 1174, 1228 |
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Maher, S.; Choudhary, M.I.; Saleem, F.; Rasheed, S.; Waheed, I.; Halim, S.A.; Azeem, M.; Abdullah, I.B.; Froeyen, M.; Mirza, M.U.; et al. Isolation of Antidiabetic Withanolides from Withania coagulans Dunal and Their In Vitro and In Silico Validation. Biology 2020, 9, 197. https://doi.org/10.3390/biology9080197
Maher S, Choudhary MI, Saleem F, Rasheed S, Waheed I, Halim SA, Azeem M, Abdullah IB, Froeyen M, Mirza MU, et al. Isolation of Antidiabetic Withanolides from Withania coagulans Dunal and Their In Vitro and In Silico Validation. Biology. 2020; 9(8):197. https://doi.org/10.3390/biology9080197
Chicago/Turabian StyleMaher, Saima, M. Iqbal Choudhary, Farooq Saleem, Saima Rasheed, Imran Waheed, Sobia Ahsan Halim, Muhammad Azeem, Iskandar Bin Abdullah, Matheus Froeyen, Muhammad Usman Mirza, and et al. 2020. "Isolation of Antidiabetic Withanolides from Withania coagulans Dunal and Their In Vitro and In Silico Validation" Biology 9, no. 8: 197. https://doi.org/10.3390/biology9080197