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

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• 作者：Elisa Nuti ; Francesca Casalini ; Salvatore Santamaria ; Pamela Gabelloni ; Sara Bendinelli ; Eleonora Da Pozzo ; Barbara Costa ; Luciana Marinelli ; Valeria La Pietra ; Ettore Novellino ; M. Margarida Bernardo ; Rafael Fridman ; Federico Da Settimo ; Claudia Martini ; Arm ; o Rossello
• 关键词：Matrix metalloproteinase inhibitors ; Hydroxamic acids ; Anti-glioma agents ; MMP-2 ; MMP-9 ; MMP-25
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：July 2011
• 年：2011
• 卷：46
• 期：7
• 页码：2617-2629
• 全文大小：1572 K

文摘

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.