Design, synthesis and biological study of pinacolyl boronate-substituted stilbenes as novel lipogenic inhibitors

Bhaskar C. Das, Xiaoping Zhao, Xiang Ying Tang, Fajun Yang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

A pilot library of novel 4,4,5,5-tetramethyl-2-(4-substitutedstyrylphenyl)- 1,3,2 dioxaborolane derivatives has been synthesized. 4-(4,4,5,5-Tetramethyl-1, 3,2-dioxaboratophenyl)-methyl triphenylphosphonium bromide 3 was treated with various aldehydes in the presence of 3 equiv of tBuONa in DMF, and stirred at room temperature for 4-6 h to yield the corresponding boron-containing stilbene derivatives in 71-94% yields. Several of them, including BF102 and BF175, have the lipogenesis inhibitory effect by suppressing lipogenic gene expression in mammalian hepatocytes. Further, BF102 also inhibits cholesterol biosynthesis by suppressing HMG-CoA reductase gene expression in hepatocytes. Interestingly, our preliminary in vivo data suggests that BF102 has no significant toxicity in mice at the highest possible dose we can administered. Thus, BF102 is a potential lead for the next generation of lipid-lowering drugs.

Original languageEnglish (US)
Pages (from-to)5638-5641
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number18
DOIs
StatePublished - Sep 15 2011

Fingerprint

Stilbenes
methyl bromide
Gene expression
Hepatocytes
Derivatives
Hydroxymethylglutaryl CoA Reductases
Gene Expression
Lipogenesis
Boron
Biosynthesis
Bromides
Aldehydes
Libraries
Toxicity
Cholesterol
Lipids
Temperature
Pharmaceutical Preparations
Lead

Keywords

  • Boron-containing stilbene derivatives
  • Lipid-lowering drugs
  • Lipogenic inhibitors
  • Sterol regulatory element binding proteins (SREBPs)
  • Wittig reaction

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Design, synthesis and biological study of pinacolyl boronate-substituted stilbenes as novel lipogenic inhibitors. / Das, Bhaskar C.; Zhao, Xiaoping; Tang, Xiang Ying; Yang, Fajun.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 21, No. 18, 15.09.2011, p. 5638-5641.

Research output: Contribution to journalArticle

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