Design and synthesis of a vialinin A analog with a potent inhibitory activity of TNF-α production and its transformation into a couple of bioprobes.

Abstract

Vialinin A (1) is an extremely potent inhibitor against tumor necrosis factor (TNF)-α production in rat basophilic leukemia (RBL-2H3) cells. This Letter describes the design and synthesis of its advanced analog, 5',6'-dimethyl-1,1':4'1″-terphenyl-2',3',4,4″-tetraol (2) with a comparable inhibitory activity (IC(50)=0.02 nM) to that of 1. The synthesis involved double Suzuki-Miyaura coupling as a key step, and required only five steps from commercially available 3,4-dimethylphenol. For identification of the target molecule, fluorescent and biotinylated derivatives of 2 were prepared through a 'click' coupling process.

• Authors: Yue Qi Ye, Jun-ichi Onose, Naoki Abe, Hiroyuki Koshino, Shunya Takahashi
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 22 Issue 7 Pg. 2385-7 (Apr 01 2012) ISSN: 1464-3405 [Electronic] England
• PMID: 22410084 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Molecular Probes
• Terphenyl Compounds
• Tumor Necrosis Factor-alpha
• Xylenes
• vialinin A
• 3,4-dimethylphenol

Topics

• Animals
• Biotinylation
• Cell Line, Tumor
• Drug Design
• Fluorescence
• Leukemia (metabolism, pathology)
• Molecular Probes (chemical synthesis)
• Molecular Structure
• Rats
• Terphenyl Compounds (chemical synthesis, pharmacology)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, biosynthesis)
• Xylenes (chemistry)