J Food Bioact

Journal of Food Bioactives, ISSN 2637-8752 print, 2637-8779 online

Journal website www.isnff-jfb.com

Original Research

Volume 23, September 2023, pages 58-67

In Silico Evaluation of Nutri-Pharmacological Potentials of Phytochemicals in Sorghum (Sorghum bicolor) Grains

Figure 2. Interaction of the binding poses. (a) gallic acid and alpha-(1,3)-fucosyltransferase 7. (b) p-coumaric acid and aldose reductase. (c) p-coumaric acid and carbonic anhydrase 1. (d) trans-resveratrol and carbonic anhydrase 1. (e) Apigenin and aldose reductase. (f) Luteolinidin and aldose reductase. (g) Apigenin and xanthine dehydrogenase. (h) Naringenin and estrogen receptor

Figure 3. Protein-ligand complex simulation results (a) RMSD of gallic acid and alpha-(1,3)-fucosyltransferase. (b) RMSF of alpha-(1,3)-fucosyltransferase. (c) Interaction profile of the contact between gallic acid and alpha-(1,3)-fucosyltransferase. (d) RMSD of p-coumaric acid and aldose reductase. (e) RMSF of aldose reductase. (f) Interaction profile of the contact between p-coumaric acid and aldose reductase.

**Table 1.** Predicted ADME for phytochemical constituents of sorghum grain
SN	Ligand	PUBCHEM ID	MW	MR	TPSA (Å²)	LOGP	ESOL LOGS	ESOL CLASS	GIA	BBB	P-GP	CYPS INHIBITOR	LOG Kp (CM/S)	BS	SA
Physicochemical properties: Molecular weight (MW), Molar Refractivity (MR), Total polar surface area (TPSA). Pharmacokinetics: Gastrointestinal absorption (GIA), Blood-brain barrier (BBB), P-glycoprotein (P-gp) substrate, Inhibition of Cytochrome P450 (CYPs) type CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4, Skin permeation (Log Kp). Water Solubility: ESOL Log S, ESOL Class. Lipophilicity: Consensus Log P. Medicinal Chemistry: Synthetic accessibility (SA). Druglikeness: Bioavailability Score (BS).
1	Protocatechuic acid	528594	154.12	37.45	77.76	0.65	−1.85	Very Soluble	High	No	No	CYP3A4	−6.42	0.56	1.07
2	p-hydroxybenzoic acid	135	138.12	35.42	57.53	1.05	−2.07	Soluble	High	Yes	No	None	−6.02	0.85	1.00
3	Vanillic acid	8468	168.15	41.92	66.76	1.08	−2.02	Soluble	High	No	No	None	−6.31	0.85	1.42
4	p-coumaric acid.	1549106	164.16	45.13	57.53	1.26	−2.02	Soluble	High	Yes	No	None	−6.26	0.85	1.61
5	Ferulic acid	445858	194.18	51.63	66.76	1.36	−2.11	Soluble	High	Yes	No	None	−6.41	0.85	1.93
6	Gallic acid	24721416	170.12	39.47	97.99	0.21	−164	Soluble	High	No	No	None	−6.84	0.56	1.22
7	Caffeic acid	154911	180.16	47.16	77.76	0.93	−1.89	Very Soluble	High	No	No	None	−6.58	0.56	1.81
8	Cinnamic acid	53729554	148.16	43.11	37.30	1.79	−2.37	Soluble	High	Yes	No	None	−5.69	0.85	1.67
9	Salicyclic acid.	46782907	138.12	35.42	57.53	1.24	−2.50	Soluble	High	Yes	No	None	−5.54	0.85	1.00
10	Syringic acid	10742			75.99	0.99	−1.84	Very Soluble	High	No	No	None	−6.77	0.56	1.70
11	Sinapic acid	637775	224.21	58.12	75.99	1.31	−2.16	Soluble	High	No	No	None	−6.00	0.56	2.17
12	Apigeninidin.	159360	271.24	74.15	94.06	0.85	−2.94	Soluble	High	No	Yes	CYP1A2	−6.95	0.55	2.92
13	Luteolinidin.	441701	270.24	73.99	90.90	2.11	−3.94	Soluble	High	No	No	CYP1A2, CYP2D6	−5.80	0.55	2.96
14	Apigenin.	528044	272.25	71.57	86.99	1.84	−3.49	Soluble	High	No	Yes	CYP1A2, CYP2D6, CYP3A4	−6.17	0.55	3.01
15	Luteolin	5280445	288.25	73.59	1.45	1.45	−3.26	Soluble	High	No	Yes	CYP1A2, CYP2D6, CYP3A4	−6.62	0.55	3.11
16	Trans-resveratrol	71684637	390.38	100	139.84	0.62	−2.90	Soluble	High	No	Yes	None	−7.95	0.55	2.02
17	Naringenin	932	272.25	71.57	86.99	1.84	−3.49	Soluble	High	No	Yes	CYP1A2, CYP3A4	−6.17	0.55	3.01

Table 1. Predicted ADME for phytochemical constituents of sorghum grain

Ligand

PUBCHEM ID

TPSA (Å²)

LOGP

ESOL LOGS

ESOL CLASS

GIA

BBB

P-GP

CYPS INHIBITOR

LOG Kp (CM/S)

Physicochemical properties: Molecular weight (MW), Molar Refractivity (MR), Total polar surface area (TPSA). Pharmacokinetics: Gastrointestinal absorption (GIA), Blood-brain barrier (BBB), P-glycoprotein (P-gp) substrate, Inhibition of Cytochrome P450 (CYPs) type CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4, Skin permeation (Log Kp). Water Solubility: ESOL Log S, ESOL Class. Lipophilicity: Consensus Log P. Medicinal Chemistry: Synthetic accessibility (SA). Druglikeness: Bioavailability Score (BS).

Protocatechuic acid

528594

154.12

37.45

77.76

0.65

−1.85

Very Soluble

High

CYP3A4

−6.42

0.56

1.07

p-hydroxybenzoic acid

135

138.12

35.42

57.53

1.05

−2.07

Soluble

High

Yes

None

−6.02

0.85

1.00

Vanillic acid

8468

168.15

41.92

66.76

1.08

−2.02

Soluble

High

None

−6.31

0.85

1.42

p-coumaric acid.

1549106

164.16

45.13

57.53

1.26

−2.02

Soluble

High

Yes

None

−6.26

0.85

1.61

Ferulic acid

445858

194.18

51.63

66.76

1.36

−2.11

Soluble

High

Yes

None

−6.41

0.85

1.93

Gallic acid

24721416

170.12

39.47

97.99

0.21

−164

Soluble

High

None

−6.84

0.56

1.22

Caffeic acid

154911

180.16

47.16

77.76

0.93

−1.89

Very Soluble

High

None

−6.58

0.56

1.81

Cinnamic acid

53729554

148.16

43.11

37.30

1.79

−2.37

Soluble

High

Yes

None

−5.69

0.85

1.67

Salicyclic acid.

46782907

138.12

35.42

57.53

1.24

−2.50

Soluble

High

Yes

None

−5.54

0.85

1.00

Syringic acid

10742

75.99

0.99

−1.84

Very Soluble

High

None

−6.77

0.56

1.70

Sinapic acid

637775

224.21

58.12

75.99

1.31

−2.16

Soluble

High

None

−6.00

0.56

2.17

Apigeninidin.

159360

271.24

74.15

94.06

0.85

−2.94

Soluble

High

Yes

CYP1A2

−6.95

0.55

2.92

Luteolinidin.

441701

270.24

73.99

90.90

2.11

−3.94

Soluble

High

CYP1A2, CYP2D6

−5.80

0.55

2.96

Apigenin.

528044

272.25

71.57

86.99

1.84

−3.49

Soluble

High

Yes

CYP1A2, CYP2D6, CYP3A4

−6.17

0.55

3.01

Luteolin

5280445

288.25

73.59

1.45

−3.26

Soluble

High

Yes

CYP1A2, CYP2D6, CYP3A4

−6.62

0.55

3.11

Trans-resveratrol

71684637

390.38

100

139.84

0.62

−2.90

Soluble

High

Yes

None

−7.95

0.55

2.02

Naringenin

932

272.25

71.57

86.99

1.84

−3.49

Soluble

High

Yes

CYP1A2, CYP3A4

−6.17

0.55

3.01

Table 2. Target prediction results for phytochemical constituents of sorghum grain

Ligands

% Probability of Predicted Targets

A. Carbon anhydrase I/II/VI/VII/XII (P00915/P00918/P23280/P43166/O43570). B. Carbon anhydrase III/IV/VA/VB/IX/XI/XIII/XIV (P07451/P22748/P35218/Q16790/Q8N1Q1/Q9ULX7), C. Aldose reductase (P15121), D. Estrogen receptor (Q92731), E. Macrophage migration inhibitory factor (P14174), F. Alpha (1–3)-fucosyltransferase7 (Q11130), G. Arachidonate 5-lioxygenase (P09917), H. Matrix metaloprotenase9 (P14780), I. Matrix metaloprotenase1 (P03956), J. Matrix metaloprotenase2 (P08253). K. Protein-tyrosine phosphatase 1B (P18031). L. Hydroxycarboxylic acid receptor (Q8TDS4). M. Lymphocyte differentiation antigen (P28907). N. NADPH Oxidase 4 (Q9NPH5). O. Cyclin-dependent kinase 5 (Q00535). P. Xanthine dehydrogenase (P47989).

Protocatechuic acid

p-hydroxy benzoic acid

100

Vanillic acid

p-coumaric acid

100

Ferulic acid

Gallic acid

100

Caffeic acid

Trans resveratrol

100

Salicylic acid

100

Syringic acid

100

Sinapic acid

Luteolinidin

100

Apigenin

100

Luteolin

Naringenin

Salicyclic acid

100

Cinnamic acid

Table 3. Molecular docking results

Protein

Binding Affinity Score(kcal.mol⁻¹)

p-Coumaric acid

Gallic acid

Trans-Resveratrol

Apigenin

Luteolinidin

Naringenin

Docking parameter: Arachidonate 5-lioxygenase [Center: −4.57, 2.552, −4.052; Size: 126, 106, 126; Spacing 0.867]. Aldose reductase [Center: 1.346, 2.385, 0.255; Size:126, 126, 126; Spacing: 0.400]. Carbon anhydrase I [Center: 36.650, 14.797, −13.116; Size:126, 126, 126; Spacing: 0.375]. Alpha (1–3) fucosynltransferase 7 [Center: 0.064, 2.743, 7.051; Size: 76, 70, 126; Spacing: 1.000]. Carbon anhydrase IV [Center: −3.911, 2.015, −4.599; Size: 126, 126, 68; Spacing: 0.844]. Carbon anhydrase XII [Center: −6.047, 0.271, −6.751; Size:126, 120, 126; Spacing: 0.536].

Arachidonate 5-lioxygenase

−5.620

Aldose reductase

−7.759

−10.430

−10.500

Carbon anhydrase I

−5.554

−5.982

Alpha (1–3) fucosynltransferase 7

−5.512

Carbon anhydrase IV

−5.163

Carbon anhydrase XII

−6.328

Estrogen receptor

−7.513

−6.648

−6.778

NADPH oxidase 4

−8.287

Cyclin dependent kinase 5

−8.366

Xanthine dehydrogenase

−9.196

**Table 4.** : Prime MMGBSA binding energy of interaction of p-coumaric acid and aldose reductase and gallic acid with alpha-(1,3)-fucosyltransferase 7, before and after molecular dynamics simulation
Complex	Simulation Time (ns)	MMGBSA ΔG^bind (kcal.mol⁻¹)
Legend: Covalent: Covalent binding energy. Coulomb: Coulomb energy. Lipo: Lipophilic energy. Hbond: Hydrogen bonding energy. Packing: Pi-pi packing correction. Solv GB: Generalized Born electrostatic solvation energy. vdW: Van der Waals energy. Total: Total energy (Prime energy).
p-Coumaric acid and aldose reductase	0	−13.980	1.333	−1.308	−22.041	−0.002	12.445	−33.076	−56.631
100	−16.204	5.018	−1.244	−21.909	−0.002	12.689	−31.892	−53.546
Gallic acid and alpha-(1,3)-fucosyltransferase 7	0	−19.226	2.005	−0.554	−8.601	−2.273	18.761	−19.743	−29.632
100	−14.336	2.594	−0.845	−7.264	−0.767	10.884	−18.929	−28.663

Table 4. : Prime MMGBSA binding energy of interaction of p-coumaric acid and aldose reductase and gallic acid with alpha-(1,3)-fucosyltransferase 7, before and after molecular dynamics simulation

Complex

Simulation Time (ns)

MMGBSA ΔG^bind (kcal.mol⁻¹)

Coulomb

Covalent

Hbond

Lipo

Packing

Solv_GB

vdW

G^bind (Total)

Legend: Covalent: Covalent binding energy. Coulomb: Coulomb energy. Lipo: Lipophilic energy. Hbond: Hydrogen bonding energy. Packing: Pi-pi packing correction. Solv GB: Generalized Born electrostatic solvation energy. vdW: Van der Waals energy. Total: Total energy (Prime energy).

p-Coumaric acid and aldose reductase

−13.980

1.333

−1.308

−22.041

−0.002

12.445

−33.076

−56.631

100

−16.204

5.018

−1.244

−21.909

−0.002

12.689

−31.892

−53.546

Gallic acid and alpha-(1,3)-fucosyltransferase 7

−19.226

2.005

−0.554

−8.601

−2.273

18.761

−19.743

−29.632

100

−14.336

2.594

−0.845

−7.264

−0.767

10.884

−18.929

−28.663