A New Class of Highly Potent Matrix Metalloproteinase Inhibitors Based on Triazole-Substituted Hydroxamates: (Radio)Synthesis and in Vitro and First in Vivo Evaluation

2012 ◽  
Vol 55 (10) ◽  
pp. 4714-4727 ◽  
Author(s):  
Verena Hugenberg ◽  
Hans-Jörg Breyholz ◽  
Burkhard Riemann ◽  
Sven Hermann ◽  
Otmar Schober ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Matrix Metalloproteinase Inhibitors ◽  
In Vivo Evaluation ◽  
New Class ◽  
Metalloproteinase Inhibitors

scholarly journals Plant-Derived Purification, Chemical Synthesis, and In Vitro/In Vivo Evaluation of a Resveratrol Dimer, Viniferin, as an HCV Replication Inhibitor

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 890 ◽  
Author(s):  
Sungjin Lee ◽  
Karabasappa Mailar ◽  
Mi Il Kim ◽  
Minkyung Park ◽  
Jiseon Kim ◽  
...  
Keyword(s):  
Water Solubility ◽  
Synthesis Method ◽  
Drug Candidate ◽  
In Vivo Evaluation ◽  
New Class ◽  
Pharmacokinetic Properties ◽  
Viral Helicase ◽  
Further Development

Oligostilbenoid compounds, a group of resveratrol multimers, display several anti-microbial activities through the neutralization of cytotoxic oxidants, and by inhibiting essential host and viral enzymes. In our previous study, we identified a series of oligostilbenoid compounds as potent hepatitis C virus (HCV) replication inhibitors. In particular, vitisin B, a resveratrol tetramer, exhibited the most dramatic anti-HCV activity (EC50 = 6 nM and CC50 > 10 μM) via the disruption of the viral helicase NS3 (IC50 = 3 nM). However, its further development as an HCV drug candidate was halted due to its intrinsic drawbacks, such as poor stability, low water solubility, and restricted in vivo absorption. In order to overcome these limitations, we focused on (+)-ε-viniferin, a resveratrol dimer, as an alternative. We prepared three different versions of (+)-ε-viniferin, including one which was extracted from the grapevine root (EVF) and two which were chemically synthesized with either penta-acetylation (SVF-5Ac) or no acetylation (SVF) using a newly established synthesis method. We confirmed their anti-HCV replication activities and minimal cytotoxicity by using genotype 1b and 2a HCV replicon cells. Their anti-HCV replication action also translated into a significant reduction of viral protein expression. Anti-HCV NS3 helicase activity by EVF was also verified in vitro. Finally, we demonstrated that SVF has improved pharmacokinetic properties over vitisin B. Overall, the favorable antiviral and pharmacokinetic properties of these three versions of viniferin warrant their further study as members of a promising new class of anti-HCV therapeutics.

scholarly journals Triple-Helical Transition State Analogues:  A New Class of Selective Matrix Metalloproteinase Inhibitors

2007 ◽  
Vol 129 (34) ◽  
pp. 10408-10417 ◽  
Author(s):  
Janelle Lauer-Fields ◽  
Keith Brew ◽  
John K. Whitehead ◽  
Shunzi Li ◽  
Robert P. Hammer ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Transition State ◽  
Matrix Metalloproteinase Inhibitors ◽  
New Class ◽  
Transition State Analogues ◽  
Metalloproteinase Inhibitors

scholarly journals Radiolabeled Selective Matrix Metalloproteinase 13 (MMP-13) Inhibitors: (Radio)Syntheses and in Vitro and First in Vivo Evaluation

2016 ◽  
Vol 60 (1) ◽  
pp. 307-321 ◽  
Author(s):  
Verena Hugenberg ◽  
Stefan Wagner ◽  
Klaus Kopka ◽  
Michael Schäfers ◽  
Robert C. Schuit ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
In Vivo Evaluation ◽  
Matrix Metalloproteinase 13

scholarly journals Bisphosfonate matrix metalloproteinase inhibitors for the treatment of periodontitis: An in vitro study

2018 ◽  
Author(s):  
Marianna De Colli ◽  
Paolo Tortorella ◽  
Mariangela Agamennone ◽  
Cristina Campestre ◽  
Fulvio Loiodice ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
In Vitro Study ◽  
Vitro Study ◽  
Matrix Metalloproteinase Inhibitors ◽  
Metalloproteinase Inhibitors
Sign in / Sign up

Export Citation Format

Share Document