Abstract
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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► MMP-2, MMP-9 and MMP-25 have been recognized to be highly expressed in gliomas. ► A series of sulfonamido-based hydroxamates was designed and synthesized. ► Derivative
5a was found to have nanomolar activity toward MMP-2, MMP-9 and MMP-25. ► This compound also proved to have anti-invasive activity on U87MG glioma cell line.