2. Academic Validation
  3. Synthesis and biological evaluation of novel benzofuroxan-based pyrrolidine hydroxamates as matrix metalloproteinase inhibitors with nitric oxide releasing activity

Synthesis and biological evaluation of novel benzofuroxan-based pyrrolidine hydroxamates as matrix metalloproteinase inhibitors with nitric oxide releasing activity

  • Bioorg Med Chem. 2018 Aug 15;26(15):4363-4374. doi: 10.1016/j.bmc.2018.06.023.
Hao Zhang 1,  Xuejian Wang 2,  Jing Mao 1,  Yongxue Huang 3,  Wenfang Xu 4,  Yu Duan 5,  Jian Zhang 6
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, School of Pharmacy, Weifang Medical University, Weifang, Shandong 261053, PR China.
  • 2 Department of Pharmacology, School of Pharmacy, Weifang Medical University, Weifang, Shandong 261053, PR China.
  • 3 Weifang Bochuang International Biological Medicinal Institute, Weifang, Shandong, 261061, PR China.
  • 4 Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong 250012, PR China.
  • 5 Department of Medicinal Chemistry, School of Pharmacy, Weifang Medical University, Weifang, Shandong 261053, PR China. Electronic address: duanyu@wfmc.edu.cn.
  • 6 Department of Medicinal Chemistry, School of Pharmacy, Weifang Medical University, Weifang, Shandong 261053, PR China. Electronic address: zhangjian_3323@163.com.
PMID: 30093347 DOI: 10.1016/j.bmc.2018.06.023
Abstract

On the basis of the strategy of "multifunctional drugs", a series of novel matrix metalloproteinase inhibitors (MMPIs) containing benzofuroxan scaffold as a nitric oxide donor were designed, synthesized and evaluated. All synthesized compounds, especially 16a, exhibited potent MMP-2,9 inhibitory activities, anti-proliferative activities and could produce high levels of NO in Hela cells. They were also evaluated for both of their anti-invasion and anti-angiogenesis effects. Furthermore, compared with LY52, 16a demonstrated competitive antitumor activity in vivo. These hybrid NO-MMPIs might offer suitable scaffolds to develop valuable MMP inhibitors for the further discovery of novel anti-cancer drugs.

Keywords

Benzofuroxan; MMP inhibitor; Multifunctional drugs; Nitric oxide; Synthesis.

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