Identification of 11-Hydroxytephrosin and Torosaflavone A as Potential Inhibitors of 3-Phosphoinositide-Dependent Protein Kinase 1 (PDPK1): Toward Anticancer Drug Discovery
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods and Materials
2.1. Computer Environment and Web Resources
2.2. Receptor Preparation
2.3. Databases Used for Screening
2.4. Molecular Docking-Based Virtual Screening
2.5. ADMET Properties of Compounds
2.6. PASS Analysis
2.7. MD Simulations
2.8. Principal Component Analysis and Free Energy Landscapes
3. Results and Discussion
3.1. Molecular Docking-Based Virtual Screening
3.2. ADMET Properties of Compounds
3.3. PASS Analysis
3.4. Interaction Analysis
3.5. MD Simulations
3.5.1. Structural Changes and Compactness
3.5.2. Dynamics of Hydrogen Bonds
3.5.3. Principal Component Analysis and Free Energy Landscapes
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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S. No. | Compound ID | Affinity (kcal/mol) |
---|---|---|
1. | CID_24901683 | −11.6 |
2. | CID_3822 | −10.8 |
3. | CID_442851 | −10.5 |
4. | CID_101277405 | −10.4 |
5. | CID_44257658 | −10.3 |
6. | CID_13846202 | −10.2 |
7. | CID_4970 | −10.2 |
8. | CID_101746 | −10.2 |
9. | CID_5245667 | −10.1 |
10. | CID_102060338 | −9.9 |
11. | CID_44257628 | −9.9 |
12. | CID_73393 | −9.8 |
13. | CID_480799 | −9.8 |
14. | CID_102267534 | −9.8 |
15. | CID_120734 | −9.7 |
16. | CID_440583 | −9.7 |
17. | CID_196979 | −9.7 |
18. | CID_4437370 | −9.7 |
19. | CID_10925304 | −9.7 |
20. | CID_5318619 | −9.7 |
21. | CID_14033985 | −9.7 |
22. | CASID_53777-78-9 | −9.6 |
23. | CID_6770 | −9.6 |
24. | CASID_22296-77-1 | −9.6 |
25. | CID_124069 | −9.6 |
26. | CID_147329 | −9.6 |
27. | CID_124050 | −9.6 |
28. | CID_443716 | −9.6 |
29. | CID_197775 | −9.6 |
30. | CID_601058 | −9.6 |
31. | CID_641765 | −9.6 |
32. | CID_5281353 | −9.6 |
33. | CID_5316096 | −9.6 |
34. | CID_5281406 | −9.6 |
35. | CID_101277371 | −9.6 |
36. | CID_101667973 | −9.6 |
37. | CASID_13241-28-6 | −9.5 |
38. | CID_120698 | −9.5 |
39. | CID_114909 | −9.5 |
40. | CID_5459059 | −9.5 |
41. | CID_6510278 | −9.5 |
42. | CID_5281867 | −9.5 |
43. | CASID_74148-50-8 | −9.4 |
44. | CID_101595 | −9.4 |
45. | CID_146680 | −9.4 |
46. | CID_10336244 | −9.4 |
47. | CID_5281809 | −9.3 |
48. | CASID_94418-50-5 | −9.3 |
49. | CASID_64191-02-2 | −9.2 |
50. | CID_5154 | −9.2 |
51. | LY333531 | −8.3 |
Compound ID | Compound Name | GI Absorption | Water Solubility (log mol/L) | BBB Permeability (log BB) | CYP2D6 Inhibitor | OCT2 Substrate | AMES |
---|---|---|---|---|---|---|---|
CID_5318619 | Isoononin | High | −3.39 | −1.27 | No | No | No |
CID_44257658 | Torosaflavone A | High | −2.90 | −1.37 | No | No | No |
CID_13846202 | 11-Hydroxytephrosin | High | −3.89 | −0.18 | No | No | No |
LY333531 | Ruboxistaurin | High | −4.81 | −0.48 | No | No | Yes |
Compound | Pa | Pi | Biological Activity |
---|---|---|---|
11-Hydroxytephrosin | 0.934 | 0.004 | Antineoplastic |
0.904 | 0.003 | Antineoplastic (non-small cell lung cancer) | |
0.857 | 0.003 | Prostate cancer treatment | |
0.822 | 0.003 | Antineoplastic (ovarian cancer) | |
0.799 | 0.004 | Chemopreventive | |
0.775 | 0.014 | TP53 expression enhancer | |
0.654 | 0.020 | Apoptosis agonist | |
0.644 | 0.016 | Kinase inhibitor | |
0.542 | 0.005 | Antioxidant | |
0.540 | 0.015 | Antineoplastic (breast cancer) | |
Torosaflavone A | 0.929 | 0.005 | Membrane integrity agonist |
0.889 | 0.006 | TP53 expression enhancer | |
0.860 | 0.006 | Antineoplastic | |
0.840 | 0.003 | Chemopreventive | |
0.832 | 0.003 | Cardioprotectant | |
0.827 | 0.005 | Kinase inhibitor | |
0.821 | 0.005 | Anticarcinogenic | |
0.800 | 0.004 | Hepatoprotectant | |
0.730 | 0.012 | Apoptosis agonist | |
0.725 | 0.009 | Antifungal | |
LY333531 (ruboxistaurin) | 0.869 | 0.007 | Antineurotic |
0.823 | 0.009 | Antineoplastic | |
0.788 | 0.004 | Chemo preventive | |
0.745 | 0.011 | Apoptosis agonist | |
0.720 | 0.044 | Hepatoprotectant | |
0.710 | 0.012 | TP53 expression enhancer | |
0.707 | 0.010 | Kinase inhibitor | |
0.699 | 0.008 | Anticarcinogenic | |
0.638 | 0.004 | Antidiabetic | |
0.612 | 0.010 | Antioxidant |
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Atiya, A.; Alhumaydhi, F.A.; Sharaf, S.E.; Al Abdulmonem, W.; Elasbali, A.M.; Al Enazi, M.M.; Shamsi, A.; Jawaid, T.; Alghamdi, B.S.; Hashem, A.M.; et al. Identification of 11-Hydroxytephrosin and Torosaflavone A as Potential Inhibitors of 3-Phosphoinositide-Dependent Protein Kinase 1 (PDPK1): Toward Anticancer Drug Discovery. Biology 2022, 11, 1230. https://doi.org/10.3390/biology11081230
Atiya A, Alhumaydhi FA, Sharaf SE, Al Abdulmonem W, Elasbali AM, Al Enazi MM, Shamsi A, Jawaid T, Alghamdi BS, Hashem AM, et al. Identification of 11-Hydroxytephrosin and Torosaflavone A as Potential Inhibitors of 3-Phosphoinositide-Dependent Protein Kinase 1 (PDPK1): Toward Anticancer Drug Discovery. Biology. 2022; 11(8):1230. https://doi.org/10.3390/biology11081230
Chicago/Turabian StyleAtiya, Akhtar, Fahad A. Alhumaydhi, Sharaf E. Sharaf, Waleed Al Abdulmonem, Abdelbaset Mohamed Elasbali, Maher M. Al Enazi, Anas Shamsi, Talha Jawaid, Badrah S. Alghamdi, Anwar M. Hashem, and et al. 2022. "Identification of 11-Hydroxytephrosin and Torosaflavone A as Potential Inhibitors of 3-Phosphoinositide-Dependent Protein Kinase 1 (PDPK1): Toward Anticancer Drug Discovery" Biology 11, no. 8: 1230. https://doi.org/10.3390/biology11081230