Forschung & Innovation
Publikationen
Tributyltin propionate and tributyltin salicylate represent novel RXR ligands
PMU Autor*innen
Jakub Kollar, Daniela Schuster
Alle Autor*innen
Dana Macejova, Jakub Kollar, Zdenek Dvorak, Daniela Schuster, Julius Brtko
Fachzeitschrift
TOXICOLOGY IN VITRO
Kurzfassung
Several organometallic trialkyltins or triaryltins are known to act as retinoid X receptor (RXR) agonists, which were also reported to exert eminent cytotoxic properties. In the present study, binding properties of tributyltin propionate (TBT-P) and tributyltin salicylate (TBT-S) in RXR alpha molecule were theoretically investigated using docking in Schro<spacing diaeresis>dinger small molecule drug discovery suite. Our data has shown that TBT-P and TBT-S bind in the binding pocket of RXR alpha and represent novel RXR agonists. In vitro data has shown that both TBT-P and TBT-S exert transcriptional activity under basal and ligand-activated conditions through RXR-nuclear thyroid hormone receptor (TR) heterodimer in the human reporter cell line for the assessment of thyroid receptor transcriptional activity (PZ-TR). In the human reporter cell line, enabling sensitive and selective identification of nuclear dihydroxyvitamin D3 receptor (VDR) agonists (IZ-VDRE), TBT-P and TBT-S did not exert any transcriptional activity through VDR under basal and ligand-activated conditions, which is in agreement with the properties of the non-permissive type of RXR-VDR heterodimer. Our in silico and in vitro data demonstrate that both organometallic compounds TBT-P and TBT-S represent new nuclear retinoid X receptor agonists.
Keywords
Retinoid X receptor ligands, Thyroid hormone receptors, Transcriptional activity, Tributyltin propionate, Tributyltin salicylate, Vitamin D(3)receptor