Synthesis and biological evaluation in U87MG glioma cells of (ethynylthiophene)sulfonamido-based hydroxamates as matrix metalloproteinase inhibitors.

Published on Jul 1, 2011in European Journal of Medicinal Chemistry5.572
· DOI :10.1016/J.EJMECH.2011.03.033
Elisa Nuti25
Estimated H-index: 25
(UniPi: University of Pisa),
Francesca Casalini10
Estimated H-index: 10
(UniPi: University of Pisa)
+ 12 AuthorsArmando Rossello28
Estimated H-index: 28
(UniPi: University of Pisa)
Matrix metalloproteinases (MMPs) are important factors in gliomas since these enzymes facilitate invasion into the surrounding brain and participate in neovascularization. In particular, the gelatinases (MMP-2 and MMP-9), and more recently MMP-25, have been shown to be highly expressed in gliomas and have been associated with disease progression. Thus, inhibition of these MMPs may represent a promising non-cytotoxic approach to glioma treatment. We report herein the synthesis and biological evaluation of a series of 4-butylphenyl(ethynylthiophene)sulfonamido-based hydroxamates. Among the new compounds tested, a promising derivative, 5a, was identified, which exhibits nanomolar inhibition of MMP-2, MMP-9, and MMP-25, but weak inhibitory activity toward other members of the MMP family. This compound also exhibited anti-invasive activity of U87MG glioblastoma cells at nanomolar concentrations, without affecting cell viability.
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