Molecular docking and assessment of thiacalix[4]arene and sulfonylcalix[4]arene as a platform for designing glutathione S-transferase inhibitors

Authors

  • Yu. V. Shulga Institute of Bioorganic Chemistry and Petrochemistry of NAS of Ukraine, Nizhyn State University named after Nikolai Gogol, Ukraine
  • O. L. Kobzar Institute of Bioorganic Chemistry and Petrochemistry of NAS of Ukraine, Ukraine
  • I. M. Mischenko Institute of Bioorganic Chemistry and Petrochemistry of NAS of Ukraine, Ukraine
  • V. Yu. Tanchuk Institute of Bioorganic Chemistry and Petrochemistry of NAS of Ukraine, Ukraine
  • V. V. Sychoveev Nizhyn State University named after Nikolai Gogol, Ukraine
  • V. I. Kalchenko Institute of Organic Chemistry of the NAS of Ukraine, Ukraine
  • A. I. Vovk Institute of Bioorganic Chemistry and Petrochemistry of NAS of Ukraine, Ukraine

DOI:

https://doi.org/10.24959/ophcj.18.942

Keywords:

calix[4]arene, thiacalix[4]arene, sulfonylcalix[4]arene, glutathione S-transferase, inhibition, molecular docking, molecular dynamics

Abstract

It is known that overexpression of isozymes of glutathione S-transferase family is one of the causes for the resistance of cancer cells to the action of drugs. Therefore, inhibitors of these enzymes can be considered as potential drugs.
Aim. To assess in silico calix[4]arene, thiacalix[4]arene, and sulfonyl alkyl[4]arene as a molecular platform for designing inhibitors of glutathione S-transferase.
Results and discussion. Docking models of complexes of glutathione S-transferase with α-hydroxymethylphosphonate derivatives of calix[4]arene, thiacalix[4]arene, and sulfonylcalix[4]arene were calculated and analyzed. The binding models obtained by AutoDock 4.2 program were assessed by the molecular dynamics simulations. It has been shown that sulfonyl groups of the sulfonylcalix[4]arene macrocycle can be involved in additional stabilization of the enzyme-inhibitor complex. In addition, the affinity of the inhibitors to the enzyme depends on the stereoisomeric α-hydroxymethylphosphonate residues located at the upper rim of the macrocycle.
Experimental part. Molecular docking of macrocyclic compounds to the active site region of glutathione S-transferase was performed using AutoDock 4.2 and AutoDock Vina. Molecular dynamics was modeled using NAMD 2.10 program.
Conclusions. It has been determined that sulfonylcalix[4]arene can be a promising molecular platform for designing inhibitors of glutathione S-transferase.

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References

  1. Slonchak, A. M., Obolenska, M. Yu. (2009). Ukrainskyi biokhimichnyi zhurnal, 81 (1), 5–11.
  2. Hayes, J. D., Flanagan, J. U., Jowsey, I. R. (2005). Glutathione transferases. Annual Review of Pharmacology and Toxicology, 45 (1), 51–88.
  3. doi: 10.1146/annurev.pharmtox.45.120403.095857
  4. Mathew, N., Kalyanasundaram, M., Balaraman, K. (2006). GlutathioneS–transferase (GST) inhibitors. Expert Opinion on Therapeutic Patents, 16 (4), 431–444. doi: 10.1517/13543776.16.4.431
  5. Koob, M., Dekant, W. (1991). Bioactivation of xenobiotics by formation of toxic glutathione conjugates. Chemico–Biological Interactions, 77 (2), 107–136. doi: 10.1016/0009–2797(91)90068–i
  6. Strange, R. C., Spiteri, M. A., Ramachandran, S., Fryer, A. A. (2001). Glutathione–S–transferase family of enzymes. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 482 (1–2), 21–26. doi: 10.1016/s0027–5107(01)00206–8
  7. Wang, W., Ballatori, N. (1998). Endogenous glutathione conjugates: occurrence and biological functions. Pharmacological reviews, 50 (3), 335–352.
  8. Dann, A. T., Kenyon, A. P., Seed, P. T., Poston, L., Shennan, A. H., Tribe, R. M. (2004). GlutathioneS–transferase and liver function in intrahepatic cholestasis of pregnancy and pruritus gravidarum. Hepatology, 40 (6), 1406–1414. doi: 10.1002/hep.20473
  9. Townsend, D. M., Tew, K. D. (2003). The role of glutathione–S–transferase in anti–cancer drug resistance. Oncogene, 22 (47), 7369–7375. doi: 10.1038/sj.onc.1206940
  10. Piaggi, S., Raggi, C., Corti, A., Pitzalis, E., Mascherpa, M. C., Saviozzi, M., Casini, A. F. (2010). Glutathione transferase omega 1–1 (GSTO1–1) plays an anti–apoptotic role in cell resistance to cisplatin toxicity. Carcinogenesis, 31 (5), 804–811. doi: 10.1093/carcin/bgq031
  11. Wang, Z., Liang, S., Lian, X., Liu, L., Zhao, S., Xuan, Q., Zhang, Q. (2015). Identification of proteins responsible for adriamycin resistance in breast cancer cells using proteomics analysis. Scientific Reports, 5 (1). doi: 10.1038/srep09301
  12. Peters, W. H., Roelofs H. M. (1992). Biochemical characterization of resistance to mitoxantrone and adriamycin in Caco–2 human colon adenocarcinoma cells: a possible role for glutathione S–transferases. Cancer Research, 52 (1), 1886–1890.
  13. Townsend, D. M., Tew, K. D. (2003). The role of glutathione–S–transferase in anti–cancer drug resistance. Oncogene, 22 (47), 7369–7375. doi: 10.1038/sj.onc.1206940
  14. Ricci, G., De Maria, F., Antonini, G. et al. (2005). Electrostatic association of glutathione transferase to the nuclear membrane. Journal of Biological Chemistry, 280 (3), 263–271.
  15. Van Zanden, J. J., Ben Hamman, O., van Iersel, M. L. P. S., Boeren, S., Cnubben, N. H. P., Lo Bello, M., Rietjens, I. M. C. M. (2003). Inhibition of human glutathione S–transferase P1–1 by the flavonoid quercetin. Chemico–Biological Interactions, 145 (2), 139–148. doi: 10.1016/s0009–2797(02)00250–8
  16. Yang, X., Liu, G., Li, H., Zhang, Y., Song, D., Li, C., Zhao, G. (2010). Novel Oxadiazole Analogues Derived from Ethacrynic Acid: Design, Synthesis, and Structure−Activity Relationships in Inhibiting the Activity of GlutathioneS–Transferase P1–1 and Cancer Cell Proliferation. Journal of Medicinal Chemistry, 53 (3), 1015–1022. doi: 10.1021/jm9011565
  17. Schultz, M., Dutta, S., Tew, K. D. (1997). Inhibitors of glutathione S–transferases as therapeutic agents. Advanced Drug Delivery Reviews, 26 (2–3), 91–104. doi: 10.1016/s0169–409x(97)00029–x
  18. Burg, D., Hameetman, L., Filippov, D. V., van der Marel, G. A., Mulder, G. J. (2002). Inhibition of glutathione S–transferase in rat hepatocytes by a glycine–tetrazole modified S–alkyl–GSH analogue. Bioorganic & Medicinal Chemistry Letters, 12 (12), 1579–1582. doi: 10.1016/s0960–894x(02)00247–0
  19. Kunze, T., Heps, S. (2000). Phosphono analogs of glutathione: inhibition of glutathione transferases, metabolic stability, and uptake by cancer cells. Biochemical Pharmacology, 59 (8), 973–981. doi: 10.1016/s0006–2952(99)00401–3
  20. Calix[4]arene–α–hydroxyphosphonic acids.Synthesis, stereochemistry, and inhibition of glutathione S–transferase. (2012). Arkivoc, 2012 (4), 278. doi: 10.3998/ark.5550190.0013.421
  21. Trush, V. V., Tanchuk, V. Y., Cherenok, S. O., Kalchenko, V. I., Vovk, A. I. (2014). Calix[4]arene α–hydroxymethylphosphonic acids as potential inhibitors of protein tyrosine phosphatases. Žurnal Organìčnoï Ta Farmacevtičnoï Hìmìï, 12 (1(45)), 39–42. doi: 10.24959/ophcj.14.782
  22. Trush, V., Cherenok, S., Tanchuk, V. et al. (2015). Evaluation of inhibition of protein tyrosine phosphatase 1B by calixarene–based α–ketophosphonic acids. Chemical Biology Letters, 2 (1), 1–5.
  23. Vovk, A. I., Kononets, L. A., Tanchuk, V. Y., Drapailo, A. B., Kalchenko, V. I., Kukhar, V. P. (2009). Thiacalix[4]arene as molecular platform for design of alkaline phosphatase inhibitors. Journal of Inclusion Phenomena and Macrocyclic Chemistry, 66 (3–4), 271–277. doi: 10.1007/s10847–009–9607–9
  24. Vovk, A. I., Kononets, L. A., Tanchuk, V. Y., Cherenok, S. O., Drapailo, A. B., Kalchenko, V. I., Kukhar, V. P. (2010). Inhibition of Yersinia protein tyrosine phosphatase by phosphonate derivatives of calixarenes. Bioorganic & Medicinal Chemistry Letters, 20 (2), 483–487. doi: 10.1016/j.bmcl.2009.11.126
  25. Trush, V. V., Tanchuk, V. Yu., Kononets, L. A. et al. (2012). Dopovidi Natsionalnoi akademii nauk Ukrainy, 3, 145–151.
  26. Buldenko, V., Kobzar, O., Trush, V., Drapailo, A., Kalchenko, V. (2017). Sulfonyl–bridged Calix[4]arene as an Inhibitor of Protein Tyrosine Phosphatases. French–Ukrainian Journal of Chemistry, 5 (2), 144–151. doi: 10.17721/fujcv5i2p144–151 26.
  27. Buldenko, V. M., Kononets, L. A., Kobzar, O. L., Drapailo, A. B., Vyshnevsky, S. G., Kalchenko, V. I., Vovk, A. I. (2017). The inhibitory potential of calixarenes against nucleotide pyrophosphatase/phosphodiesterase 1. Žurnal Organìčnoï Ta Farmacevtičnoï Hìmìï, 15 (4(60)), 41–47. doi: 10.24959/ophcj.17.928
  28. Gutsche, C. D. (1998). Calixarenes revisited. The Royal Society of Chemistry, 2 (4), 56–61.
  29. Alonso, H., Bliznyuk, A. A., Gready, J. E. (2006). Combining docking and molecular dynamic simulations in drug design. Medicinal Research Reviews, 26 (5), 531–568. doi: 10.1002/med.20067
  30. Oakley, A. J., Lo Bello, M., Nuccetelli, M., Mazzetti, A. P., Parker, M. W. (1999). The ligandin (non–substrate) binding site of human pi class glutathione transferase is located in the electrophile binding site (H–site). Journal of Molecular Biology, 291 (4), 913–926. doi: 10.1006/jmbi.1999.3029
  31. Morris, M., Huey, R., Olson A. (2008) Using autodock for ligand–receptor docking. TSRI, 8 (14), 1–8.
  32. Trott, O., Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. Journal of Computational Chemistry, 31 (2), 455–461. doi: 10.1002/jcc.21334
  33. ChemAxon (2009). Available at: http: // www. Chemaxon. com.
  34. Hanwell, M. D., Curtis, D. E., Lonie, D. C., Vandermeersch, T., Zurek, E., Hutchison, G. R. (2012). Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. Journal of Cheminformatics, 4 (1), 17. doi: 10.1186/1758–2946–4–17
  35. Phillips, J. C., Braun, R., Wang, W., Gumbart, J., Tajkhorshid, E., Villa, E., Schulten, K. (2005). Scalable molecular dynamics with NAMD. Journal of Computational Chemistry, 26 (16), 1781–1802. doi: 10.1002/jcc.20289
  36. Zoete, V., Cuendet, M. A., Grosdidier, A., Michielin, O. (2011). SwissParam: A fast force field generation tool for small organic molecules. Journal of Computational Chemistry, 32 (11), 2359–2368. doi: 10.1002/jcc.21816
  37. Humphrey, W., Dalke, A., Schulten, K. (1996). VMD: Visual molecular dynamics. Journal of Molecular Graphics, 14 (1), 33–38. doi: 10.1016/0263–7855(96)00018–5

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Published

2018-06-08

How to Cite

(1)
Shulga, Y. V.; Kobzar, O. L.; Mischenko, I. M.; Tanchuk, V. Y.; Sychoveev, V. V.; Kalchenko, V. I.; Vovk, A. I. Molecular Docking and Assessment of thiacalix[4]arene and sulfonylcalix[4]arene As a Platform for Designing Glutathione S-Transferase Inhibitors. J. Org. Pharm. Chem. 2018, 16, 42-48.

Issue

Vol. 16 No. 2(62) (2018)

Section

Original Researches

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