Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 144, Issue -, Pages 612-625Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2017.12.047
Keywords
Histone deacetylases; Nitric oxide; Multitarget drugs; Muscle differentiation; Vasodilatation
Categories
Funding
- LOEWE Cell & Gene Therapy Center (LOEWE-CGT) Goethe University Frankfurt
- Deutsche Forschungsgemeinschaft Program [SFB834]
- LOEWE CGT grant [III L 5 - 518/17.004]
- DFG (German Research Foundation), Excellence Cluster Cardio Pulmonary System
- LOEWE-Forschungszentrum fur Zell-und Gentherapie, gefor-dert durch das Hessische Ministerium fur Wissenschaft und Kunst. Aktenzeichen [III L 5 - 491 518/17.004]
- University of Turin
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HDAC inhibitors and NO donors have already revealed independently their broad therapeutic potential in pathologic contexts. Here we further investigated the power of their combination in a single hybrid molecule. Nitrooxy groups or substituted furoxan derivatives were joined to the alpha-position of the pyridine ring of the selective class I HDAC inhibitor MS-275. Biochemical analysis showed that the association with the dinitrooxy compound 31 or the furoxan derivative 16 gives hybrid compounds the ability to preserve the single moiety activities. The two new hybrid molecules were then tested in a muscle differentiation assay. The hybrid compound bearing the moiety 31 promoted the formation of large myotubes characterized by highly multinucleated fibers, possibly due to a stimulation of myoblast fusion, as implicated by the strong induction of myomaker expression. Thanks to their unique biological features, these compounds may represent new therapeutic tools for cardiovascular, neuromuscular and inflammatory diseases. (C) 2017 Elsevier Masson SAS. All rights reserved.
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