On the interactions of leflunomide and teriflunomide within receptor cavity -NMR studies and energy calculations

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• 作者：Jacek Kujawski ; Marek K. Bernard ; El?bieta Jod?owska…
• 关键词：DFT calculations ; Hydrogen bond ; Leflunomide ; NMR calculations ; Teriflunomide
• 刊名：Journal of Molecular Modeling
• 出版年：2015
• 出版时间：May 2015
• 年：2015
• 卷：21
• 期：5
• 全文大小：2,290 KB
• 参考文献：1. Kaplan, MJ (2001) Curr Opin Investig D 2: pp. 222
  2. Behrens, F, Finkenwirth, C, Pavelka, K, ?tolfa, J, ?ipek-Dolnicar, A, Tha?i, D, Burkhardt, H (2013) Arthritis Care Res 65: pp. 464 CrossRef
  3. Kellner, H, Bornholdt, K, Hein, G (2010) Clin Rheumatol 29: pp. 913 CrossRef
  4. Kalgutkar, AS, Nguyen, HT, Vaz, AD, Doan, A, Dalvie, DK, McLeod, DG, Murray, JC (2003) Drug Metab Dispos 31: pp. 1240 CrossRef
  5. McLean, JE, Neidhardt, EA, Grossman, TH, Hedstrom, L (2001) Biochemistry 40: pp. 2194 CrossRef
  6. O'Connor, PW, Li, D, Freedman, MS, Bar-or, A, Rice, GPA, Confavreux, C, Paty, DW, Stewart, JA, Scheyer, R (2006) Neurology 66: pp. 894 CrossRef
  7. Baumann, P, Mandl-Weber, S, V?lkl, A, Adam, C, Bumeder, I, Oduncu, F, Schmidmaier, R (2009) Mol Cancer Ther 8: pp. 366 CrossRef
  8. Zhu, S, Yan, X, Xiang, Z, Ding, HF, Cui, H (2013) PLoS ONE 8: pp. e7155
  9. M?czyński, M, Ryng, S, Artym, J, Kocieba, M, Zimecki, M, Brudnik, K, Jodkowski, JT (2014) Acta Pol Pharm 71: pp. 71
  10. Browne, DL (2014) Angew Chem Int Ed 53: pp. 1482 CrossRef
  11. Metro, T-X, Bonnamour, J, Reidon, T, Sarpoulet, J, Martinez, J, Lamaty, F (2012) Chem Commun 48: pp. 11781 CrossRef
  12. Dai, J-J, Fang, C, Xiao, B, Yi, J, Xu, J, Liu, Z-J, Lu, X, Liu, L, Fu, Y (2013) J Am Chem Soc 135: pp. 8436 CrossRef
  13. Ivashkin, P, Lemonnier, G, Cousin, J, Gregoire, V, Labar, D, Jubault, P, Pannecoucke, X (2014) Chem Eur J 20: pp. 9514 CrossRef
  14. Liu, S, Neidhardt, EA, Grossman, TH, Ocain, T, Clardy, J (2000) Structure 8: pp. 25 CrossRef
  15. Leban, J, Saeb, W, Garcia, G, Baumgartner, R, Kramer, B (2004) Bioorg Med Chem Lett 14: pp. 55 CrossRef
  16. Davies, M, Heikkil?, T, McConkey, GA, Fishwick, CW, Parsons, MR, Johnson, AP (2009) J Med Chem 52: pp. 2683 CrossRef
  17. Panek, JJ, Jezierska, A, Mierzwicki, K, Latajka, Z, Koll, A (2005) J Chem Inf Model 45: pp. 39 CrossRef
  18. Kujawski, J, Doskocz, M, Popielarska, H, Myka, A, Drabińska, B, Kruk, J, Bernard, MK (2013) J Mol Struct 1047: pp. 292 CrossRef
  19. Tukiendorf A, Nishizawa Y, Morii H, Durlach J (2007) Magnesium intake and hepatic cancer in new perspectives in magnesium research. Springer, Berlin, p 155
  20. Raissi, H, Mollania, F (2014) Eur J Pharm Sci 56: pp. 37 CrossRef
  21. Faragher, RJ, Motto, JM, Kaminski, MA, Schwan, AL (2003) J Label Compd Radiopharm 46: pp. 613 CrossRef
  22. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA Jr, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam NJ, Klene
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Computer Applications in Chemistry
  Biomedicine
  Molecular Medicine
  Health Informatics and Administration
  Life Sciences
  Computer Application in Life Sciences
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：0948-5023

文摘

Leflunomide is a disease-modifying antirheumatic drug with antiinflammatory and immunosuppressive activity used for the treatment of psoriatic and rheumatoid arthritis. It undergoes rapid metabolization to teriflunomide, a metabolite that is responsible for the biological activity of leflunomide. Continuing our investigations on the interactions of biologically important azahetarenes with the environment, we focused on leflunomide and its active metabolite, teriflunomide, considering the interactions teriflunomide–amino acid within the target protein (dihydroorotate dehydrogenase) using density functional theory, as well as ONIOM techniques. The results of theoretical studies have shown that the interactions of teriflunomide with tyrosine and arginine involve principally the amide fragment of teriflunomide. The presence of the internal hydrogen bond between (Z)-teriflunomide carbonyl oxygen and enolic hydroxyl decreases the interaction strength between teriflunomide and tyrosine or arginine. Even the E isomer of teriflunomide would usually provide a stronger interaction teriflunomide—amino acid than the Z isomer with the internal hydrogen bond. Graphical Abstract The interactions of leflunomide and teriflunomide within receptor cavity?/em>