Citation: Xiang-Cong WANG, Mao-Cheng YANG, Mo-Xuan ZHANG, Yin-Jie HU, Zhong-Hua WANG, Fan-Hong WU. 3D-QSAR, Molecular Docking and Molecular Dynamics Simulations of 3-Phenylsulfonylaminopyridine Derivatives as Novel PI3Kα Inhibitors[J]. Chinese Journal of Structural Chemistry, ;2021, 40(12): 1567-1585. doi: 10.14102/j.cnki.0254-5861.2011-3216 shu

3D-QSAR, Molecular Docking and Molecular Dynamics Simulations of 3-Phenylsulfonylaminopyridine Derivatives as Novel PI3Kα Inhibitors

Xiang-Cong WANG ^a ,
Mao-Cheng YANG ^a ,
Mo-Xuan ZHANG ^a ,
Yin-Jie HU ^a ,
Zhong-Hua WANG ^{a, b,,} ,
Fan-Hong WU ^{a, b,,}

a.
School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201418, China
b.
Shanghai Engineering Research Center of Green Fluoropharmaceutial Technology, Shanghai 201418, China

Corresponding author: Zhong-Hua WANG, wzhsit@163.com Fan-Hong WU, wfh@sit.edu.cn
Received Date: 13 April 2021
Accepted Date: 2 June 2021

Figures(10)

The p110α, catalytic subunit of PI3Kα, was the primary phosphoinositide 3-kinases (PI3Ks) isoform involved in oncogenic RTK signaling and tumorigenesis. In this study, the three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamics simulation were employed to study the binding mode between 3-phenylsulfonylaminopyridine derivatives and PI3Kα. The stable and reliable 3D-QSAR models were constructed based on the application of the comparative molecular field analysis (CoMFA) model (q² = 0.704, r² = 0.994) and comparative molecular similarity index analysis (CoMSIA) model (q² = 0.804, r² = 0.996). The contour maps illustrated relationship between structure and biological activity. The conformation obtained after MD simulation was more stable than the docked conformation. MD simulation was performed in a more realistic environment, and was much closer to physiological conditions. As a result, five novel PI3Kα inhibitors were designed with better biological activity than the template compound 8.
- PI3K inhibitor,
- 3D-QSAR,
- molecular docking,
- molecular dynamics simulation
1. [1]
  Fry, M. J. Structure, regulation and function of phosphoinositide 3-kinases. Biochim. Biophys. Acta 1994, 1226, 237−268. doi: 10.1016/0925-4439(94)90036-1
2. [2]
  Soler, A.; Angulo-Urarte, A.; Graupera, M. PI3K at the crossroads of tumor angiogenesis signaling pathways. Mol. Cell Oncol. 2015, 2, e975624−10. doi: 10.4161/23723556.2014.975624
3. [3]
  Bader, A. G.; Kang, S.; Zhao, L.; Vogt, P. K. Oncogenic PI3K deregulates transcription and translation. Nat. Rev. Cancer 2005, 5, 921−929. doi: 10.1038/nrc1753
4. [4]
  Engelman, J. A.; Luo, J.; Cantley, L. C. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat. Rev. Genet. 2006, 7, 606−619.
5. [5]
  Rewcastle, G. W.; Gamage, S. A.; Flanagan, J. U.; Kendall, J. D.; Denny, W. A.; Baguley, B. C.; Buchanan, C. M.; Chao, M.; Kestell, P.; Kolekar, S.; Lee, W. J.; Lill, C. L.; Malik, A.; Singh, R.; Jamieson, S. M.; Shepherd, P. R. Synthesis and biological evaluation of novel phosphatidylinositol 3-kinase inhibitors: solubilized 4-substituted benzimidazole analogs of 2-(difluoromethyl)-1-[4, 6-di(4-morpholinyl)-1, 3, 5-triazin-2-yl]-1H-benzimidazole (ZSTK474). Eur. J. Med. Chem. 2013, 64, 137−147. doi: 10.1016/j.ejmech.2013.03.038
6. [6]
  Vanhaesebroeck, B.; Guillermet-Guibert, J.; Graupera, M.; Bilanges, B. The emerging mechanisms of isoform-specific PI3K signalling. Nat. Rev. Mol. Cell Biol. 2010, 11, 329−341.
7. [7]
  Paddock, M. N.; Field, S. J.; Cantley, L. C. Treating cancer with phosphatidylinositol-3-kinase inhibitors: increasing efficacy and overcoming resistance. J. Lipid Res. 2019, 60, 747−752. doi: 10.1194/jlr.S092130
8. [8]
  Thorpe, L. M.; Yuzugullu, H.; Zhao, J. J. PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting. Nat. Rev. Cancer 2015, 15, 7−24. doi: 10.1038/nrc3860
9. [9]
  Swat, W.; Montgrain, V.; Doggett, T. A.; Douangpanya, J.; Puri, K.; Vermi, W.; Diacovo, T. G. Essential role of PI3Kdelta and PI3Kgamma in thymocyte survival. Blood 2006, 107, 2415−2422. doi: 10.1182/blood-2005-08-3300
10. [10]
  Yuan, T. L.; Cantley, L. C. PI3K pathway alterations in cancer: variations on a theme. Oncogen. 2008, 27, 5497−5510. doi: 10.1038/onc.2008.245
11. [11]
  Rewcastle, G. W.; Gamage, S. A.; Flanagan, J. U.; Frederick, R.; Denny, W. A.; Baguley, B. C.; Kestell, P.; Singh, R.; Kendall, J. D.; Marshall, E. S.; Lill, C. L.; Lee, W. J.; Kolekar, S.; Buchanan, C. M.; Jamieson, S. M.; Shepherd, P. R. Synthesis and biological evaluation of novel analogues of the pan class Ⅰ phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(difluoromethyl)-1-[4, 6-di(4-morpholinyl)-1, 3, 5-triazin-2-yl]-1H-benzimidazole (ZSTK474). J. Med. Chem. 2011, 54, 7105−7126. doi: 10.1021/jm200688y
12. [12]
  Falasca, M.; Hughes, W. E.; Dominguez, V.; Sala, G.; Fostira, F.; Fang, M. Q.; Cazzolli, R.; Shepherd, P. R.; James, D. E.; Maffucci, T. The role of phosphoinositide 3-kinase C2alpha in insulin signaling. J. Biol. Chem. 2007, 282, 28226−28236. doi: 10.1074/jbc.M704357200
13. [13]
  Liu, X.; Xu, Y.; Zhou, Q.; Chen, M.; Zhang, Y.; Liang, H.; Zhao, J.; Zhong, W.; Wang, M. PI3K in cancer: its structure, activation modes and role in shaping tumor microenvironment. Future Oncology 2018, 14, 665−674. doi: 10.2217/fon-2017-0588
14. [14]
  Singh, P.; Dar, M. S.; Dar, M. J. p110alpha and p110beta isoforms of PI3K signaling: are they two sides of the same coin? FEBS Lett. 2016, 590, 3071−3082. doi: 10.1002/1873-3468.12377
15. [15]
  Zhu, J.; Jia, L.; Jiang, Y.; Yu, Q.; Xu, L.; Cai, Y.; Chen, Y.; Li, H.; Gang, H.; Liang, W.; Jin, J. Integrated molecular modeling techniques to reveal selective mechanisms of inhibitors to PI3Kδ with marketed Idelalisib. Chem. Biol. Drug Des. 2021, 97, 1158−1169. doi: 10.1111/cbdd.13838
16. [16]
  Scott, W. J.; Hentemann, M. F.; Rowley, R. B.; Bull, C. O.; Jenkins, S.; Bullion, A. M.; Johnson, J.; Redman, A.; Robbins, A. H.; Esler, W.; Fracasso, R. P.; Garrison, T.; Hamilton, M.; Michels, M.; Wood, J. E.; Wilkie, D. P.; Xiao, H.; Levy, J.; Stasik, E.; Liu, N.; Schaefer, M.; Brands, M.; Lefranc, J. Discovery and SAR of novel 2, 3-dihydroimidazo[1, 2-c]quinazoline PI3K inhibitors: identification of copanlisib (BAY 80-6946). ChemMedChem. 2016, 11, 1517−1530. doi: 10.1002/cmdc.201600148
17. [17]
  Garces, A. E.; Stocks, M. J. ClassⅠPI3K clinical candidates and recent inhibitor design strategies: a medicinal chemistry perspective. J. Med. Chem. 2019, 62, 4815−4850. doi: 10.1021/acs.jmedchem.8b01492
18. [18]
  Furet, P.; Guagnano, V.; Fairhurst, R. A.; Imbach-Weese, P.; Bruce, I.; Knapp, M.; Fritsch, C.; Blasco, F.; Blanz, J.; Aichholz, R.; Hamon, J.; Fabbro, D.; Caravatti, G. Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. Bioorg. Med. Chem. Lett. 2013, 23, 3741−3748. doi: 10.1016/j.bmcl.2013.05.007
19. [19]
  Cramer, R. D.; Patterson, D. E.; Bunce, J. D. Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J. Am. Chem. Soc. 1988, 110, 5959−5967. doi: 10.1021/ja00226a005
20. [20]
  Klebe, G.; Abraham, U.; Mietzner, T. Molecular similarity indices in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity. J. Med. Chem. 1994, 37, 4130−46. doi: 10.1021/jm00050a010
21. [21]
  Han, F.; Lin, S.; Liu, P.; Liu, X.; Tao, J.; Deng, X.; Yi, C.; Xu, H. Discovery of a novel series of thienopyrimidine as highly potent and selective PI3K inhibitors. ACS Med. Chem. Lett. 2015, 6, 434−438. doi: 10.1021/ml5005014
22. [22]
  Lin, S.; Jin, J.; Liu, Y.; Tian, H.; Zhang, Y.; Fu, R.; Zhang, J.; Wang, M.; Du, T.; Ji, M.; Wu, D.; Zhang, K.; Sheng, L.; Li, Y.; Chen, X.; Xu, H. Discovery of 4-methylquinazoline based PI3K inhibitors for the potential treatment of idiopathic pulmonary fibrosis. J. Med. Chem. 2019, 62, 8873−8879. doi: 10.1021/acs.jmedchem.9b00969
23. [23]
  Lin, S.; Wang, C.; Ji, M.; Wu, D.; Lv, Y.; Sheng, L.; Han, F.; Dong, Y.; Zhang, K.; Yang, Y.; Li, Y.; Chen, X.; Xu, H. Discovery of new thienopyrimidine derivatives as potent and orally efficacious phosphoinositide 3-kinase inhibitors. Bioorg. Med. Chem. 2018, 26, 637−646. doi: 10.1016/j.bmc.2017.12.025
24. [24]
  Lin, S.; Han, F.; Liu, P.; Tao, J.; Zhong, X.; Liu, X.; Yi, C.; Xu, H. Identification of novel 7-amino-5-methyl-1, 6-naphthyridin-2(1H)-one derivatives as potent PI3K/mTOR dual inhibitors. Bioorg. Med. Chem. Lett. 2014, 24, 790−793. doi: 10.1016/j.bmcl.2013.12.112
25. [25]
  Han, F.; Lin, S.; Liu, P.; Tao, J.; Yi, C.; Xu, H. Synthesis and structure-activity relationships of PI3K/mTOR dual inhibitors from a series of 2-amino-4-methylpyrido[2, 3-d]pyrimidine derivatives. Bioorg. Med. Chem. Lett. 2014, 24, 4538−4541. doi: 10.1016/j.bmcl.2014.07.073
26. [26]
  Ran, T.; Lu, T.; Yuan, H. L.; Liu, H. C.; Wang, J.; Zhang, W. W.; Leng, Y.; Lin, G. W.; Zhuang, S. L.; Chen, Y. D. A selectivity study on mTOR/PI3K alpha inhibitors by homology modeling and 3D-QSAR. J. Mol. Model. 2012, 18, 171−86. doi: 10.1007/s00894-011-1034-3
27. [27]
  Yuan, H. L.; Tai, W. T.; Hu, S. H.; Liu, H. C.; Zhang, Y. M.; Yao, S. H.; Ran, T.; Lu, S.; Ke, Z. P.; Xiong, X.; Xu, J. X.; Chen, Y. D.; Lu, T. Fragment-based strategy for structural optimization in combination with 3D-QSAR. J. Comput. Aided Mol. Des. 2013, 27, 897−15. doi: 10.1007/s10822-013-9687-x
28. [28]
  Yuan, H.; Liu, H.; Liu, C. W.; Wang, F.; Zhang, Y.; Yao, S.; Ran, T.; Lu, S.; Ke, Z.; Xiong, X.; Xu, J.; Chen, Y.; Lu, T. Molecular modelling on small molecular CDK2 inhibitors: an integrated approach using a combination of molecular docking, 3D-QSAR and pharmacophore modelling. SAR QSAR Environ. Res. 2013, 24, 795−17. doi: 10.1080/1062936X.2013.815655
29. [29]
  Leng, Y.; Lu, T.; Yuan, H. L.; Liu, H. C.; Lu, S.; Zhang, W. W.; Jiang, Y. L.; Chen, Y. D. QSAR studies on imidazopyrazine derivatives as aurora a kinase inhibitors. SAR QSAR Environ. Res. 2012, 23, 705−30. doi: 10.1080/1062936X.2012.719541
30. [30]
  Lu, S.; Liu, H. C.; Chen, Y. D.; Yuan, H. L.; Sun, S. L.; Gao, Y. P.; Yang, P.; Zhang, L.; Lu, T. Combined pharmacophore modeling, docking, and 3D-QSAR studies of PLK1 inhibitors. Int. J. Mol. Sci. 2011, 12, 8713−8739. doi: 10.3390/ijms12128713
31. [31]
  Zhang, Y. M.; Liu, H. C.; Jiao, Y.; Yuan, H. L.; Wang, F. G.; Lu, S.; Yao, S. H.; Ke, Z. P.; Tai, W. T.; Jiang, Y. L.; Chen, Y. D.; Lu, T. De novo design of N-(pyridin-4-ylmethyl)aniline derivatives as KDR inhibitors: 3D-QSAR, molecular fragment replacement, protein-ligand interaction fingerprint, and ADMET prediction. Mol. Diver. 2012, 16, 787−02. doi: 10.1007/s11030-012-9405-y
32. [32]
  Roy, K. K.; Saxena, A. K. Structural basis for the β-adrenergic receptor subtype selectivity of the representative agonists and antagonists. J. Chem. Inf. Model. 2011, 51, 1405−22. doi: 10.1021/ci2000874
33. [33]
  Huang, Y. Y.; Li, Z.; Cai, Y. H.; Feng, L. J.; Wu, Y.; Li, X. S.; Luo, H. B. The molecular basis for the selectivity of tadalafil toward phosphodiesterase 5 and 6: a modeling study. J. Chem. Inf. Model. 2013, 53, 3044−53. doi: 10.1021/ci400458z
34. [34]
  Sabbah, D. A.; Vennerstrom, J. L.; Zhong, H. Z. Binding selectivity studies of phosphoinositide 3-kin-ases using free energy calculations. J. Chem. Inf. Model. 2012, 52, 3213−24. doi: 10.1021/ci3003057
35. [35]
  Chang, H. W.; Chung, F. S.; Yang, C. N. Molecular modeling of p38alpha mitogen-activated protein kinase inhibitors through 3D-QSAR and molecular dynamics simulations. J. Chem. Inf. Model. 2013, 53, 1775−86. doi: 10.1021/ci4000085
36. [36]
  Clark, M.; Cramer Ⅲ, R. D.; Van Opdenbosch, N. Validation of the general purpose tripos 5.2 force field. J. Comput. Chem. 1989, 10, 982−1012. doi: 10.1002/jcc.540100804
37. [37]
  Gasteiger, J.; Marsili, M. Iterative partial equalization of orbital electronegativity – a rapid access to atomic charges. Tetrahedron 1980, 36, 3219−3228. doi: 10.1016/0040-4020(80)80168-2
38. [38]
  Pearlman, D. A.; Case, D. A.; Caldwell, J. W.; Ross, W. S.; Cheatham, T. E.; DeBolt, S.; Ferguson, D.; Seibel, G.; Kollman, P. AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules. Comp. Phys. Commun. 1995, 91, 1−41. doi: 10.1016/0010-4655(95)00041-D
39. [39]
  Maier, J. A.; Martinez, C.; Kasavajhala, K.; Wickstrom, L.; Hauser, K. E.; Simmerling, C. ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB. Theor. Comput. 2015, 11, 3696−3713. doi: 10.1021/acs.jctc.5b00255
40. [40]
  Miyamoto, S.; Kollman, P. A. Settle: an analytical version of the SHAKE and RATTLE algorithm for rigid water models. J. Comput. Chem. 1992, 13, 952−962. doi: 10.1002/jcc.540130805
41. [41]
  Humphrey, W.; Dalke, A.; Schulten, K. VMD-visual molecular dynamics. J. Molec. Graphics 1996, 14, 33−38. doi: 10.1016/0263-7855(96)00018-5
42. [42]
  Han, J.; Chen, Y.; Yang, C.; Liu, T.; Wang, M.; Xu, H.; Zhang, L.; Zheng, C.; Song, Y.; Zhu, J. Structure-based optimization leads to the discovery of NSC765844, a highly potent, less toxic and orally efficacious dual PI3K/mTOR inhibitor. Eur. J. Med. Chem. 2016, 122, 684−701. doi: 10.1016/j.ejmech.2016.06.030
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