Design, synthesis and biological characterization of a new class of osteogenic (1H)-quinolone derivatives
2016
Smoothened(Smo) is the signal transducer of the
Hedgehog(Hh) pathway and its stimulation is considered a potential powerful tool in
regenerative medicineto treat severe tissue injuries. Starting from GSA-10, a recently reported Hh activator acting on Smo, we have designed and synthesized a new class of
quinolone-based compounds. Modification and decoration of three different portions of the original scaffold led to compounds able to induce differentiation of multipotent mesenchymal cells into osteoblasts. The submicromolar activity of several of these new
quinolones(0.4-0.9 μM) is comparable to or better than that of SAG and
purmorphamine, two reference Smo agonists.
Structure-activity relationshipsallow identification of several molecular determinants important for the activity of these compounds.
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