Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 26, Issue 15, Pages 4363-4374Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2018.06.023
Keywords
MMP inhibitor; Nitric oxide; Benzofuroxan; Multifunctional drugs; Synthesis
Funding
- Natural Science Foundation of Shandong Province [BS2015YY016]
- Higher Educational Science and Technology Program of Shandong Province [J17KB098]
- Shandong Province Traditional Chinese Medicine Science and Technology Development Project [2015228]
- National Natural Science Foundation of China [81501683, 31600386]
- Doctoral Foundation of Weifang Medical University
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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 antiinvasion 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.
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