Chromane derivatives of small aromatic molecules: Chemoenzymatic synthesis and growth inhibitory activity on human tumor cell line LoVo WT

Bioorg Med Chem. 2009 Aug 15;17(16):6003-7. doi: 10.1016/j.bmc.2009.06.061. Epub 2009 Jul 3.

Abstract

Aromatic substrates tyrosol (p-hydroxyphenylethanol) and 2,6-dihydroxynaphthalene (2,6-DHN) were converted into chromane derivatives by means of chemoenzymatic reactions catalyzed by the aromatic prenyltransferase of bacterial origin NovQ, using dimethylallyl bromide as allylic substrate instead of the natural isoprenyl pyrophosphate substrate. Stereoselective prenylation occurred in o-position with respect to the phenol hydroxyl in both compounds. Prenylated derivatives were readily converted into chromane products via a selective 6-endo-trig cyclization involving the oxygen atom from the phenol moiety and the double bond of the prenyl substituent, a process catalyzed by FeCl(3). These findings set up the basis of a most convenient two-step, one-pot process which allows for easy recovery of the chromane products in high yields. The chromane derivatives thus obtained were tested for cytotoxicity and pro-apoptotic activity using LoVo WT cells, a line of human colon adenocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / toxicity
  • Biocatalysis
  • Cell Line, Tumor
  • Chromans / chemistry*
  • Chromans / toxicity
  • Colonic Neoplasms / drug therapy
  • Dimethylallyltranstransferase / chemistry
  • Dimethylallyltranstransferase / isolation & purification
  • Dimethylallyltranstransferase / metabolism*
  • Growth Inhibitors / biosynthesis*
  • Growth Inhibitors / chemistry
  • Growth Inhibitors / toxicity
  • Humans
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism

Substances

  • Antineoplastic Agents
  • Chromans
  • Growth Inhibitors
  • Recombinant Proteins
  • Dimethylallyltranstransferase