Table 3.
DPP-IV inhibition1 by flavonoids (IC50), their number of hydroxyl groups (OH), binding energy, inhibition constant (K i)2, H bonds involved, and π interactions.
| Flavonoids | IC50 (μM) | Number of OH groups | Binding energy (kcal/mol) | K i (μM) | H Bonds3 | π interactions |
|---|---|---|---|---|---|---|
| Positive control Diprotin A |
4.21 ± 2.01bc | 0 | −7.31 | 4.42 | TYR547:HH-UNK:O22 UNK:H28-TYR666:OH UNK:H11-GLU206:OE1 UNK:H11-GLU206:OE2 UNK:H12-GLU205:OE2 |
π-cation TYR666-UNK:N13 |
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| Berry flavonoids Cyanidin |
1.41 ± 0.25e | 5 | −5.95 | 43.43 | TRP563:HN-UNK:O15 ALA564:HN-UNK:O18 UNK:H7-TYR48:OH UNK:H11-GLY741:O |
π-π
UNK-B:TRP629 UNK-B:TRP629 UNK-B:TRP629 UNK-B:TRP629 |
|
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| Cyanidin-3-glucoside | 0.42 ± 0.09ef | 8 | −6.35 | 22.33 | PHE357:HN-UNK:O20 ARG358:HH22-UNK:O17 ARG358:HE-UNK:O27 GLU361:HN-UNK:O9 ARG669:HH21-UNK:O31 UNK:H1-PHE208:O UNK:H6-GLU361:OE1 UNK:H20-GLU206:OE1 UNK:H20-UNK:O26 |
π-cation UNK-HIS126:NE2 UNK-ARG358:NH1 UNK-ARG358:NH2 UNK:ARG358:NH1 |
|
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| Malvidin | 1.41 ± 0.44ef | 3 | −6.36 | 21.64 | ARG356:HH11-UNK:O13 ARG356:HH11-UNK:O17 ARG358:HE-UNK:O11 ARG585:HH-UNK:O14 UNK:H6-ILE405:O UNK:H14-GLU206:O |
π-π
UNK-PHE357 UNK-PHE357 π-cation UNK-ARG669:NH2 UNK-ARG669:NH1 UNK-ARG669:NH2 |
|
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| Citrus flavonoids Luteolin |
0.12 ± 0.01f | 4 | −6.26 | 25.83 | ARG358:HE-UNK:O10 GLU361:NH-UNK:O1 UNK:H1-GLU361:OE1 UNK:H6-GLU205:O UNK:H7-SER209:OG UNK:H9-UNK:O7 |
π-cation UNK-ARG669:NH2 π-sigma UNK-PHE357:CB |
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| Apigenin | 0.14 ± 0.02f | 3 | −6.14 | 31.77 | ARG356:HH11-UNK:O10 ARG358:HE-UNK:O5 GLU361:HN-UNK:O14 UNK:H4-UNK:O8 UNK:H5-GLU205:O UNK:H10-GLU205:O UNK:H10-SER209:OG |
π-cation UNK-ARG669:NH2 |
|
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| Quercetin | 2.92 ± 0.68d | 5 | −6.33 | 23.03 | ARG356:HN-UNK:O5 ARG356:HN-UNK:O3 UNK:H2-UNK:O4 UNK:H3-ARG358:O UNK:H4-GLU206:O UNK:H5-SER209:OG |
π-cation unk-ARG358:NH2 UNK-ARG358:NH2 UNK-ARG669:NH1 UNK-ARG669:NH2 |
|
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| Kaempferol | 0.49 ± 0.02ef | 4 | −6.62 | 13.99 | SER209:HG-UNK:O21 ARG356:HN-UNK:O8 PHE357:HN-UNK:O13 ARG358:HN-UNK:O13 UNK:H3-UNK:O8 UNK:H4-ARG358:O UNK:H5-GLU361:OE2 UNK:H10-SER209:OG |
π-cation UNK-ARG356:NH1 UNK-ARG358:NH1 UNK-ARG358:NH2 |
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| Flavone | 0.17 ± 0.01f | 0 | −6.64 | 13.57 | No hydrogen bonds | No π interactions |
|
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| Hesperetin | 0.28 ± 0.07ef | 3 | −6.85 | 9.57 | ARG358:HH22-UNK:O2 ARG669:HH21-UNK:O5 UNK:H2-GLU206:OE1 UNK:H1-UNK:O2 UNK:H3-ARG358:O |
π-cation UNK-ARG358:NH1 |
|
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| Naringenin | 0.24 ± 0.03ef | 3 | −6.83 | 9.90 | ARG356:HH11-UNK:O20 ARG358:HE-UNK:O10 GLU361:HN-UNK:O19 UNK:H11-GLU361:OE1 UNK:H12-UNK:O11 UNK:H10-SER209:OG |
π-cation UNK-arg358:NH1 UNK-ARG358:NH2 |
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| Eriocitrin | 10.36 ± 0.09a | 9 | −9.07 | 225.96 | ARG356:HH11-UNK:O8 PHE357:HN-UNK:O10 ARG358:HN-UNK:O10 ARG358:HE-UNK:O14 ARG429:HH22-UNK:O23 ARG669:HH21-UNK:O30 UNK:H5-ARG358:O UNK:H12-TYR585:OH UNK:H28-TYR585:OH UNK:H32-CYS551:O UNK:H20-GLU206:O UNK:H15-GLU206:O |
π-cation UNK-ARG356:NH1 |
|
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| Soy isoflavone Genistein |
0.48 ± 0.04ef | 3 | −6.5 | 17.31 | ARG356:HN-UNK:O12 PHE357:HN-UNK:O10 ARG358:HN-UNK:O10 UNK:H4-ARG358:O UNK:H4-UNK:O10 UNK:H5-GLU36:OE1 UNK:H10-GLU206:O |
π-π
PHE357-UNK π-cation UNK-ARG356:NH1 UNK-ARG358:NH1 UNK-ARG358:NH1 UNK-ARG669:NH1 |
|
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| Grape stilbenoid Resveratrol |
0.0006 ± 0.0004g | 3 | −6.54 | 15.96 | ARG669:HH21-UNK:O7 UNK:H12-SER630:OG UNK:H5-SER209:OG UNK:H4-GLU206:O |
|
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| Other flavonoids EGCG |
10.21 ± 0.75a | 8 | −4.39 | 604.91 | GLN553:HN-UNK:O32 UNK:H8-GLU206:OE1 UNK:H11-TYR666:OH UNK:H15-TYR662:OH UNK:H15-TYR585:OH |
π-π
PHE357-UNK PHE357-UNK π-cation UNK-HIS740:NE2 |
|
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| Gallic acid | 4.65 ± 0.99b | 3 | −3.96 | 1.25 | ARG356:HH11-UNK:O11 PHE357:HN-UNK:O7 ARG358:HN-UNK:O7 TRY585:HH-UNK:O10 UNK:H3-ARG358:O UNK:H5-ILE405:O UNK:H6- ILE405:O |
π-cation UNK-ARG356:NH2 |
|
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| Caffeic acid | 3.37 ± 0.14cd | 3 | −5.23 | 147.66 | ARG358:HE-UNK:O13 ARG358:HH22-UNK:O12 ARG669:HH21-UNK:O9 UNK1:H6-GLU206:OE1 UNK:H7-GLU206:OE1 |
π-π
PHE357-UNK |
1IC50 values were determined from at least two independent duplicates done in triplicate for each of the concentrations tested. Concentrations (μM) were calculated based on the molecular mass of each pure compound. Values are means ± SEM. Means with different letters in each column are significantly different for DPP-IV (P < 0.05).
2 K i values were obtained from computational docking as indicated in Materials and Methods section.
3UNK refers to phenolic compound or diprotin A.