Leflunomide is a disease-modifying antirheumatic\ndrug with antiinflammatory and immunosuppressive activity\nused for the treatment of psoriatic and rheumatoid arthritis. It\nundergoes rapid metabolization to teriflunomide, a metabolite\nthat is responsible for the biological activity of leflunomide.\nContinuing our investigations on the interactions of biologically\nimportant azahetarenes with the environment, we focused\non leflunomide and its active metabolite, teriflunomide,\nconsidering the interactions teriflunomideââ?¬â??amino acid within\nthe target protein (dihydroorotate dehydrogenase) using density\nfunctional theory, as well as ONIOM techniques. The\nresults of theoretical studies have shown that the interactions\nof teriflunomide with tyrosine and arginine involve principally\nthe amide fragment of teriflunomide. The presence of the internal\nhydrogen bond between (Z)-teriflunomide carbonyl oxygen\nand enolic hydroxyl decreases the interaction strength\nbetween teriflunomide and tyrosine or arginine. Even the E\nisomer of teriflunomide would usually provide a stronger interaction\nteriflunomideââ?¬â?amino acid than the Z isomer with\nthe internal hydrogen bond.
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