Design, synthesis, evaluation and 3D-QSAR analysis of benzosulfonamide benzenesulfonates as potent and selective inhibitors of MMP-2

被引：11

作者：

Qiu, Han-Yue ^{[1
]}

Wang, Zhong-Chang ^{[1
]}

Wang, Peng-Fei ^{[1
]}

Yan, Xiao-Qiang ^{[1
]}

Wang, Xiao-Ming ^{[1
]}

Yang, Yong-Hua ^{[1
]}

Zhu, Hai-Liang ^{[1
]}

机构：

[1] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China

来源：

RSC ADVANCES | 2014年 / 4卷 / 74期

关键词：

MATRIX-METALLOPROTEINASE INHIBITORS; CANCER; PROLIFERATION; THERAPY; S-1';

D O I：

10.1039/c4ra06438k

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A novel series of MMPIs was designed, synthesized and purified using a scaffold modification strategy. The new compounds were also evaluated for biological activity against A549, MCF-7, HepG2 and Hela as potential inhibitors of MMP-2. The most potent inhibitor against MMP-2 was compound 19 (IC50 = 0.38 mu M). Its antitumor effect is believed to be due to the induction of apoptosis, which is further confirmed by Annexin V-FITC/PI staining assay using flow cytometry analysis. Furthermore, all the compounds were evaluated for cytotoxicity against 293T. In addition, 3D-QSAR studies were conducted. The result showed that the benzosulfonamide benzenesulfonate MMPIs may prove interesting lead candidates to target MMP-2 associated tumor, where the MMP-2 domain is located extracellularly.

引用

页码：39214 / 39225

页数：12

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