Molecular Docking and Molecular Dynamics Studies of Antidiabetic Phenolic Compound Isolated from Leaf Extract of Englerophytum magalismontanum (Sond.) T.D.Penn.
Abstract
:1. Introduction
2. Results and Discussion
2.1. Plant Extraction and Biological Activities of Crude Methanol Extract and Its Fractions
2.1.1. Plant Extraction and Solvent-Solvent Fractionation of Crude Extract
2.1.2. Antioxidant Activity and TPC of Crude Extract and Its Fractions
2.1.3. α-Amylase and α-Glucosidase Inhibitory Activity of Crude Extract and Its Fraction
2.2. Isolation and Identification of the Structure of Active Compound
2.3. In Silico Activity of Acarbose and Naringenin against α-Glucosidase Receptor
2.3.1. Molecular Docking of Acarbose and Naringenin
2.3.2. Molecular Dynamics of Acarbose and Naringenin
3. Materials and Methods
3.1. Chemicals and Apparatus
3.2. Plant Materials
3.3. Plant Extraction and Bio-Assay Guided Fractionation
3.4. Characterization of Chemical Structure of Compound
3.5. Total Polyphenolic Content (TPC)
3.6. DPPH (2,2-Diphenyl-1-picrylhydrazyl) Antioxidant Assay
3.7. Enzyme Inhibitory Activity
3.7.1. α-Amylase Inhibitory Assay
3.7.2. α-Glucosidase Inhibitory Assay
3.7.3. Calculation of IC50
3.8. In Silico Assay
3.8.1. Ligand and Receptor Preparations
3.8.2. Molecular Docking
3.8.3. Molecular Dynamics
3.9. Data Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
Abbreviations
MMFF94 | molecular modeling force field developed in 1994 |
PDB ID | protein data bank identifier |
NPT | isobaric-isothermal ensemble |
PDBQT | protein data bank, partial charge (Q) and atom type (T) format |
OPLS | optimized potentials for liquid simulations |
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Extract/Fractions | DPPH Scavenging Expressed as TAE (Trolox Antioxidant Equivalent) µg/mL | Total Phenolic Content (mg GAE/g Dry Extract) |
---|---|---|
Crude methanol | 1.66 ± 0.63 a | 49.78 ± 0.40 a |
Hexane (HF) | 3.06 ± 0.77 a | 42.12 ± 1.53 b |
Chloroform (CF) | 2.99 ± 2.78 b | 53.08 ± 1.98 b |
Ethyl acetate (EF) | 2.24 ± 1.69 b | 54.41 ± 1.22 b |
Methanol (MF) | 1.51 ± 0.66 a | 56.53 ± 1.94 b |
Ascorbic acid | 0.56 ± 0.88 | ND |
Extract | 50% Inhibitory Concentration (IC50) (µg/mL) | |
---|---|---|
α-Amylase Inhibition | α-Glucosidase Inhibition | |
Crude methanol | 16.16 ± 2.23 a,c | 12.25 ± 1.03 a,b |
Fraction | ||
Hexane | 50.93 ± 0.25 b | 39.28 ± 1.02 a |
Chloroform | 60.85 ± 0.72 b | 52.24 ± 1.02 a |
Ethyl acetate | 29.18 ± 1.14 a | 25.20 ± 0.76 a |
Methanol | 10.76 ± 1.33 a,c | 12.27 ± 1.55 a,b |
MF sub-fraction | ||
MF1 | 26.84 ± 1.67 c | 58.75 ± 1.48 b |
MF2 | 36.93 ± 1.01 c | 28.63 ± 1.21 b |
MF3 | 12.49 ± 0.96 c,d | 10.19 ± 1.04 b |
MF4 | 45.11 ± 1.36 c | 27.63 ± 2.02 b,d |
MF3 sub-fraction | ||
MF3-1 | 8.79 ± 2.23 d | 6.88 ± 0.79 c |
MF3-2 | 8.71 ± 1.42 d | 7.84 ± 2.61 d |
Naringenin | 5.81 ± 2.14 d | 4.77 ± 2.99 d |
Acarbose (positive control) | 1.24 ± 1.64 | 1.92 ± 0.73 |
NMR | Spectra Signal Correlations |
---|---|
1H | δ 7.37 and 6.83 ppm, (J = 8.6 Hz, H-2′, 6′ and H-3′, 5); δ 5.87 and 5.89 ppm (J = 2.2 Hz, H-6 and H-8). 5-OH δ 5.44 (1H, dd, J = 13.0 and 3.0 Hz), δ 2.70 (1H, dd, J = 17.2 and 3.0 Hz) and δ 3.15 (1H, dd, J = 17.2 and 13.0 Hz) |
13C | δ 98.20 (C-6), δ 97.50 (C-8), δ 115.22 (C-3′ and C-5′) and δ 128.10 (C-2′ and C-6′) |
HMBC | 2JC-H and 3JC-H, δ 196.28 (C-4), δ 160.10 (C-4′), δ 166.59 (C-7), δ 164.11 (C-5), δ 163.50 (C-8a), δ 129.49 (C-1′) and δ 102.19 (C-4a). |
Compound | Binding Energy (kcal/mol) |
---|---|
Acarbose | −7.9 |
Naringenin | −7.0 |
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Olaokun, O.O.; Manonga, S.A.; Zubair, M.S.; Maulana, S.; Mkolo, N.M. Molecular Docking and Molecular Dynamics Studies of Antidiabetic Phenolic Compound Isolated from Leaf Extract of Englerophytum magalismontanum (Sond.) T.D.Penn. Molecules 2022, 27, 3175. https://doi.org/10.3390/molecules27103175
Olaokun OO, Manonga SA, Zubair MS, Maulana S, Mkolo NM. Molecular Docking and Molecular Dynamics Studies of Antidiabetic Phenolic Compound Isolated from Leaf Extract of Englerophytum magalismontanum (Sond.) T.D.Penn. Molecules. 2022; 27(10):3175. https://doi.org/10.3390/molecules27103175
Chicago/Turabian StyleOlaokun, Oyinlola Oluwunmi, Sizakele Annousca Manonga, Muhammad Sulaiman Zubair, Saipul Maulana, and Nqobile Monate Mkolo. 2022. "Molecular Docking and Molecular Dynamics Studies of Antidiabetic Phenolic Compound Isolated from Leaf Extract of Englerophytum magalismontanum (Sond.) T.D.Penn." Molecules 27, no. 10: 3175. https://doi.org/10.3390/molecules27103175