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.
|Autori:||NUTI E; CASALINI F; SANTAMARIA S; GABELLONI P; BENDINELLI S; DA POZZO E; COSTA B; MARINELLI L; LA PIETRA V; NOVELLINO E; BERNARDO M.M; FRIDMAN R; DA SETTIMO PASSETTI F; MARTINI C; ROSSELLO A|
|Titolo:||Synthesis and biological evaluation in U87MG glioma cells of (ethynylthiophene)sulfonamido-based hydroxamates as matrix metalloproteinase inhibitors|
|Anno del prodotto:||2011|
|Digital Object Identifier (DOI):||10.1016/j.ejmech.2011.03.033|
|Appare nelle tipologie:||1.1 Articolo in rivista|