Research & Innovation
Publications
Tributyltin propionate and tributyltin salicylate represent novel RXR ligands
PMU Authors
Jakub Kollar, Daniela Schuster
All Authors
Dana Macejova, Jakub Kollar, Zdenek Dvorak, Daniela Schuster, Julius Brtko
Journal association
TOXICOLOGY IN VITRO
Abstract
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