Synthesis and biological evaluation in U87MG glioma cells of (ethynylthiophene)sulfonamido-based hydroxamates as matrix metalloproteinase inhibitors.
Synthesis and biological evaluation in U87MG glioma cells of (ethynylthiophene)sulfonamido-based hydroxamates as matrix metalloproteinase inhibitors.
复制标题
DOI：
10.1016/j.ejmech.2011.03.033
复制
发表时间：
2011-07
影响因子：
6.7
通讯作者：
Rossello, Armando
中科院分区：
文献类型：
--
作者：
Nuti, Elisa;Casalini, Francesca;Santamaria, Salvatore;Gabelloni, Pamela;Bendinelli, Sara;Da Pozzo, Eleonora;Costa, Barbara;Marinelli, Luciana;La Pietra, Valeria;Novellino, Ettore;Bernardo, M. Margarida;Fridman, Rafael;Da Settimo, Federico;Martini, Claudia;Rossello, Armando
基质金属蛋白酶（MMPs）是胶质瘤的重要因素，因为这些酶有助于侵入周围的大脑并参与新生血管。特别是，明胶酶（MMP-2和MMP-9），以及最近的MMP-25，已被证明在胶质瘤中高度表达，并与疾病进展有关。因此，抑制这些MMPs可能代表了一种有希望的非细胞毒性胶质瘤治疗方法。本文报道了一系列4-丁基苯基（乙基噻吩）磺酰胺基羟基酸盐的合成和生物学评价。在测试的新化合物中，发现了一种很有前途的衍生物5a，它对MMP-2、MMP-9和MMP-25具有纳摩尔抑制作用，但对MMP家族的其他成员具有较弱的抑制活性。该化合物在纳米摩尔浓度下对U87MG胶质母细胞瘤细胞具有抗侵袭活性，且不影响细胞活力。
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 towards other members of the MMP family. This compound also exhibited anti-invasive activity of U87MG glioblastoma cells at nanomolar concentrations, without affecting cell viability.
登录
查看更多内容
影响因子：
3
作者：
Lee M;Celenza G;Boggess B;Blase J;Shi Q;Toth M;Bernardo MM;Wolter WR;Suckow MA;Hesek D;Noll BC;Fridman R;Mobashery S;Chang M
通讯作者：
Chang M
影响因子：
7.3
作者：
Becker, DP;Villamil, CI;Swearingen, CA
通讯作者：
Swearingen, CA
影响因子：
7.3
作者：
Kiyama, R;Tamura, Y;Yodo, M
通讯作者：
Yodo, M
影响因子：
7.3
作者：
Friesner, Richard A.;Murphy, Robert B.;Mainz, Daniel T.
通讯作者：
Mainz, Daniel T.
影响因子：
11.2
作者：
Krüger, A;Arlt, MJE;Fridman, R
通讯作者：
Fridman, R