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A series of bifunctional ruthenium(II) arene compounds modified with bexarotene, a retinoid that selectively activates retinoid X receptors inducing cell differentiation and apoptosis and preventing drug resistance, are described. The bexarotene is tethered to the ruthenium(II) arene fragment via an imidazole linker. Both the bexarotene-imidazole ligand and ruthenium(II) arene complexes are considerably more cytotoxic than the parent drug bexarotene. Docking studies show that the interactions of these compounds with possible targets are significantly different to the binding mode of the parent drug. (C) 2017 Elsevier B.V. All rights reserved.
Paul Joseph Dyson, Farzaneh Fadaei Tirani, Mouna Hadiji