Berry and Citrus Phenolic Compounds Inhibit Dipeptidyl Peptidase IV: Implications in Diabetes Management

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)	𝐾𝑖 (𝜇M)	H Bonds^3	𝜋 interactions
Positive control; Diprotin A	4.21 ± 2.01^bc	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
Berry flavonoids; Cyanidin	1.41 ± 0.25^e	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
Cyanidin-3-glucoside	0.42 ± 0.09^ef	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
Malvidin	1.41 ± 0.44^ef	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
Citrus flavonoids; Luteolin	0.12 ± 0.01^f	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
Apigenin	0.14 ± 0.02^f	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
Quercetin	2.92 ± 0.68^d	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
Kaempferol	0.49 ± 0.02^ef	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
Flavone	0.17 ± 0.01^f	0	−6.64	13.57	No hydrogen bonds	No 𝜋 interactions
Hesperetin	0.28 ± 0.07^ef	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
Naringenin	0.24 ± 0.03^ef	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
Eriocitrin	10.36 ± 0.09^a	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
Soy isoflavone; Genistein	0.48 ± 0.04^ef	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
Grape stilbenoid; Resveratrol	0.0006 ± 0.0004^g	3	−6.54	15.96	ARG669:HH21-UNK:O7; UNK:H12-SER630:OG; UNK:H5-SER209:OG; UNK:H4-GLU206:O
Other flavonoids; EGCG	10.21 ± 0.75^a	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
Gallic acid	4.65 ± 0.99^b	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
Caffeic acid	3.37 ± 0.14^cd	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).
²𝐾_𝑖 values were obtained from computational docking as indicated in Materials and Methods section.
³UNK refers to phenolic compound or diprotin A.