Dataset Information

Selective Binding of Cyclodextrins with Leflunomide and Its Pharmacologically Active Metabolite Teriflunomide.

ABSTRACT: The selectivity of encapsulation of leflunomide and teriflunomide by native ?-, ?- and ?-cyclodextrins was investigated through ¹H NMR and molecular modeling. Thermodynamic analysis revealed the main driving forces involved in the binding. For ?-cyclodextrin, the partial encapsulation was obtained while deep penetration was characterized for the other two cyclodextrins, where the remaining polar fragment of the molecule is located outside the macrocyclic cavity. The interactions via hydrogen bonding are responsible for high negative enthalpy and entropy changes accompanying the complexation of cyclodextrins with teriflunomide. These results were in agreement with the molecular modeling calculations, which provide a clearer picture of the involved interactions at the atomic level.

SUBMITTER: Terekhova I

PROVIDER: S-EPMC7730839 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Selective Binding of Cyclodextrins with Leflunomide and Its Pharmacologically Active Metabolite Teriflunomide.

Terekhova Irina I Kritskiy Iliya I Agafonov Mikhail M Kumeev Roman R Martínez-Cortés Carlos C Pérez-Sánchez Horacio H

International journal of molecular sciences 20201130 23

The selectivity of encapsulation of leflunomide and teriflunomide by native α-, β- and γ-cyclodextrins was investigated through <sup>1</sup>H NMR and molecular modeling. Thermodynamic analysis revealed the main driving forces involved in the binding. For α-cyclodextrin, the partial encapsulation was obtained while deep penetration was characterized for the other two cyclodextrins, where the remaining polar fragment of the molecule is located outside the macrocyclic cavity. The interactions via h ...[more]

PMID: 33265979

Similar Datasets

Project description:BACKGROUND:Leflunomide is a low-molecular-weight compound that is widely used in the treatment of rheumatoid arthritis. Although leflunomide is thought to act through the inhibition of the de novo pyrimidine synthesis, the molecular mechanism of the drug remains largely unknown. We investigated the antiarthritis effects and mechanisms of action of the active metabolite of leflunomide, A77 1726, in interleukin-1 receptor antagonist-knockout (IL-1Ra-KO) mice. METHODS:14- to 15-week-old male IL-1Ra-KO mice were treated with 10 or 30 mg/kg A77 1726 via intraperitoneal injection three times per week for 6 weeks. The effects of A77 1726 on arthritis severities were assessed by clinical scoring and histological analysis. The serum concentrations of IL-1?, tumor necrosis factor-? (TNF-?), and malondialdehyde were measured by enzyme-linked immunosorbent assay. Histologic analysis of the joints was performed using Safranin O, and immunohistochemical staining. The frequencies of interleukin-17-producing CD4+ T (Th17) cells were analyzed by flow cytometry. Heme oxygenase-1 (HO-1) expression in splenic CD4+ T cells isolated from A77 1726-treated arthritis mice were assessed by western blotting. RESULTS:A77 1726 treatment induced heme oxygenase-1 (HO-1) in Jurkat cells and primary mouse T cells. Interestingly, A77 1726 inhibited Th17 cell differentiation. In vivo, A77 1726 reduced the clinical arthritis severity of histological inflammation and cartilage destruction. The joints isolated from A77 1726-treated mice showed decreased expression of inducible nitric oxide synthase, nitrotyrosine, TNF-?, and IL-1?. The serum levels of TNF-?, IL-1?, and malondialdehyde were also decreased in A77 1726-treated mice. Whereas the number of Th17 cells in spleens was decreased in A77 1726-treated arthritis mice, a significant increase in the number of Treg cells in spleens was observed. Interestingly, HO-1 expression was significantly higher in splenic CD4+ T cells isolated from A77 1726-treated mice compared with those from vehicle-treated mice, whereas HO-1 expression of splenic non-CD4+ T cells did not differ between groups. CONCLUSION:The inhibitory effects of A77 1726 on joint inflammation and oxidative stress in autoimmune arthritis may be associated with HO-1 induction in CD4+ T cells.

Dataset Information

Selective Binding of Cyclodextrins with Leflunomide and Its Pharmacologically Active Metabolite Teriflunomide.

Publications

Selective Binding of Cyclodextrins with Leflunomide and Its Pharmacologically Active Metabolite Teriflunomide.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure