caa a22 4500 605513317 CHVBK 20210128100659.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s00894-015-2643-z doi (NATIONALLICENCE)springer-10.1007/s00894-015-2643-z On the interactions of leflunomide and teriflunomide within receptor cavity — NMR studies and energy calculations [Elektronische Daten] [Jacek Kujawski, Marek Bernard, Elżbieta Jodłowska, Kornelia Czaja, Beata Drabińska] 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 cavityᅟ The Author(s), 2015 DFT calculations nationallicence Hydrogen bond nationallicence Leflunomide nationallicence NMR calculations nationallicence Teriflunomide nationallicence Kujawski Jacek Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6 street, 60-780, Poznań, Poland aut Bernard Marek Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6 street, 60-780, Poznań, Poland aut Jodłowska Elżbieta Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6 street, 60-780, Poznań, Poland aut Czaja Kornelia Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6 street, 60-780, Poznań, Poland aut Drabińska Beata Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6 street, 60-780, Poznań, Poland aut Journal of Molecular Modeling Springer Berlin Heidelberg 21/5(2015-05-01), 1-12 1610-2940 21:5<1 2015 21 894 https://doi.org/10.1007/s00894-015-2643-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00894-015-2643-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kujawski Jacek Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6 street, 60-780, Poznań, Poland aut NATIONALLICENCE 700 1- Bernard Marek Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6 street, 60-780, Poznań, Poland aut NATIONALLICENCE 700 1- Jodłowska Elżbieta Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6 street, 60-780, Poznań, Poland aut NATIONALLICENCE 700 1- Czaja Kornelia Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6 street, 60-780, Poznań, Poland aut NATIONALLICENCE 700 1- Drabińska Beata Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Grunwaldzka 6 street, 60-780, Poznań, Poland aut NATIONALLICENCE 773 0- Journal of Molecular Modeling Springer Berlin Heidelberg 21/5(2015-05-01), 1-12 1610-2940 21:5<1 2015 21 894