Identification and Validation of Urea Transporter B Inhibitor from Apium graveolens L. Seeds In Vitro and In Silico
Abstract
:1. Introduction
2. Results and Discussion
2.1. The Activity of Different Polarity Fractions In Vitro
2.2. Characterization of the Constitutions of Apium graveolens L. Through HPLC-TOF-MS
2.3. Inhibition Activity of Compounds Against UT-B
2.4. Molecular Docking Analysis
2.5. Establishment and Validation of the Common-Feature-Based Pharmacophore (HipHop)
2.6. Assessment of UT-B with Isovaleric Acid p-tolylester by Using MDs Simulation
2.7. SwissADME Prediction of Isovaleric Acid p-tolylester
3. Materials and Methods
3.1. Chemicals, Drugs, and Reagents
3.2. Preparation of Extracts
3.3. Establishment of a Compound Library for Celery Seeds
3.4. Animals
3.5. Collection of Rat Blood and Erythrocyte Suspension Preparation
3.6. UT-B Inhibitory Activity
3.7. UPLC-TOF-MS Analysis
3.8. Molecular Docking
3.9. Pharmacophore Modeling
3.10. Molecular Dynamics Simulations
3.11. ADME Prediction
3.12. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Peak | Retention Time | Formula | [M+H]+ | [M+H]+ Calculated | Error (ppm) | Compound |
---|---|---|---|---|---|---|
1 | 6.91 | C12H16O2 | 193.1226 | 193.1229 | −1.6 | Isovaleric acid p-tolylester |
2 | 7.03 | C10H14O | 173.0942 | 173.0942 | 0.0 | Carvacrol |
3 | 8.54 | C12H16O2 | 385.2386 * | 385.2379 * | 1.8 | L-3-n-butyl-4,5-dihydrophth-alide |
4 | 8.56 | C15H24 | 205.1957 | 205.1956 | 0.5 | β-selinene |
Peak | Retention Time | Formula | [M+H]+ | [M+H]+ Calculated | Error (ppm) | Compound |
---|---|---|---|---|---|---|
1 | 3.64 | C10H16 | 273.2582 * | 273.2583 * | 0.4 | Cinene |
2 | 3.90 | C5H10O2 | 227.1260 * | 227.1259 * | 0.4 | Valeric acid |
3 | 3.89 | C9H10O | 291.1361 * | 291.1361 * | 0.0 | Allyl phenyl ether |
4 | 5.92 | C7H6O2 | 267.0638 * | 267.0633 * | 1.9 | p-Hydroxybenzaldehyde |
5 | 6.98 | C10H14O | 173.0942 | 173.0942 | 0.0 | Carvacrol |
6 | 8.11 | C18H30O2 | 279.2327 | 279.2324 | 1.1 | Linolenic acid |
7 | 8.50 | C10H16 | 273.2586 * | 273.2583 * | 0.4 | β-Myrcene |
NO. | Name | Structural | IC50/EC50 |
---|---|---|---|
1 | UTBinh-14 [45] | 0.025 μM | |
2 | PU168 [9] | 0.2 μM | |
3 | PU-1424 [17] | 0.69 μM | |
4 | 25a [20] | 0.58 μM | |
5 | CB-20 [46] | 2.01 μM |
No. | Features | Rank |
---|---|---|
1 | RHAA | 46.204 |
2 | RHAA | 46.204 |
3 | RHAA | 44.155 |
4 | RHAA | 44.155 |
5 | RHAA | 42.657 |
6 | RHAA | 42.090 |
7 | RHAA | 41.997 |
8 | RHAA | 41.102 |
9 | RHAA | 41.016 |
10 | RHAA | 40.861 |
NO. | Name | Structural | IC50/EC50 |
---|---|---|---|
1 | Phloretin [47] | 0.77 mM | |
2 | PU468 [9] | 0.80 μM | |
3 | 1H [19] | 1.60 μM | |
4 | PU-14 [15] | 0.2 μM | |
5 | PU-474 [9] | 0.28 μM | |
6 | Ureainh-101 [48] | 0.03 μM | |
7 | Ureainh-201 [48] | 0.3 μM | |
8 | Ureainh-302 [48] | 0.2 μM | |
9 | 1,2,4-Triazoloquinoxaline [18] | 2 μM | |
10 | UTA1inh-A1 [49] | 16 μM |
Time | A (%) | B (%) | Curve |
---|---|---|---|
0 | 10 | 90 | |
1.50 | 35 | 65 | 6 |
5.50 | 50 | 50 | 6 |
8.00 | 75 | 25 | 6 |
12.50 | 97 | 3 | 6 |
14.50 | 97 | 3 | 6 |
15.00 | 10 | 90 | 6 |
17.00 | 10 | 90 | 6 |
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Chen, G.; Li, X.; Pan, X.; Guo, L.; Wei, W.; Sun, X.; Wei, H.; Qin, X.; Zhang, K.; Zhang, W.; et al. Identification and Validation of Urea Transporter B Inhibitor from Apium graveolens L. Seeds In Vitro and In Silico. Molecules 2025, 30, 1540. https://doi.org/10.3390/molecules30071540
Chen G, Li X, Pan X, Guo L, Wei W, Sun X, Wei H, Qin X, Zhang K, Zhang W, et al. Identification and Validation of Urea Transporter B Inhibitor from Apium graveolens L. Seeds In Vitro and In Silico. Molecules. 2025; 30(7):1540. https://doi.org/10.3390/molecules30071540
Chicago/Turabian StyleChen, Guanzhong, Xin Li, Xinhui Pan, Li Guo, Wei Wei, Xiaoying Sun, Hongtao Wei, Xue Qin, Ke Zhang, Wei Zhang, and et al. 2025. "Identification and Validation of Urea Transporter B Inhibitor from Apium graveolens L. Seeds In Vitro and In Silico" Molecules 30, no. 7: 1540. https://doi.org/10.3390/molecules30071540
APA StyleChen, G., Li, X., Pan, X., Guo, L., Wei, W., Sun, X., Wei, H., Qin, X., Zhang, K., Zhang, W., Wei, L., Sun, P., & Yang, X. (2025). Identification and Validation of Urea Transporter B Inhibitor from Apium graveolens L. Seeds In Vitro and In Silico. Molecules, 30(7), 1540. https://doi.org/10.3390/molecules30071540