The scope of thallium nitrate oxidative cyclization of chalcones; synthesis and evaluation of isoflavone and aurone analogs for their inhibitory activity against interleukin-5

Bioorg Med Chem. 2010 Jun 15;18(12):4441-5. doi: 10.1016/j.bmc.2010.04.075. Epub 2010 Apr 26.

Abstract

The oxidative cyclization of 2'-hydroxy-6'-cyclohexylmethoxychalcones 5 using thallium (III) nitrate (TTN) in alcoholic solvents produced isoflavones 2 and (or) aurones 3 depending on the electronic nature of p-substituents on ring B. Chalcones with strong electron donating substituents (OH, OCH(3)) were exclusively converted to isoflavones 2. Chalcone with weak electron donating substituents (CH(2)CH(3)) was transformed into isoflavone 2 and the aurone 3 in approximate ratio 1:1. Chalcones with hydrogen or electron withdrawing substituents (Cl, CHO, COOCH(3), and NO(2)) formed aurones 3. Synthesized isoflavones 2 and aurones 3 were evaluated for their inhibitory activity against interleukin-5. Among them, 5-(cyclohexylmethoxy)-3-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one (2h, >100% inhibition at 50 microM, IC(50)=6.1 microM) gave most potent activity. All the aurones 3 were inactive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzofurans / chemical synthesis
  • Benzofurans / chemistry*
  • Benzofurans / pharmacology
  • Cell Line
  • Chalcones / chemistry*
  • Cyclization
  • Interleukin-5 / antagonists & inhibitors*
  • Interleukin-5 / metabolism
  • Isoflavones / chemical synthesis
  • Isoflavones / chemistry*
  • Isoflavones / pharmacology
  • Mice
  • Oxidation-Reduction
  • Structure-Activity Relationship
  • Thallium / chemistry*

Substances

  • 5-(cyclohexylmethoxy)-3-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one
  • Benzofurans
  • Chalcones
  • Interleukin-5
  • Isoflavones
  • aurone
  • Thallium
  • thallium nitrate