The first total syntheses of (±)-norphoebine, dehydrophoebine, oxophoebine, dehydrocrebanine, oxocrebanine and uthongine and their cytotoxicity against three human cancer cell lines

J Asian Nat Prod Res. 2016 Nov;18(11):1042-56. doi: 10.1080/10286020.2016.1177025. Epub 2016 May 5.

Abstract

The first total syntheses of (±)-norphoebine, dehydrophoebine, oxophoebine, dehydrocrebanine, oxocrebanine and uthongine have been achieved. The crucial step involved the formation of ring C by a microwave-assisted direct biaryl coupling to produce the aporphine skeleton in high yields. The synthetic alkaloids were evaluated for their cytotoxicity against three human cancer cell lines MCF7, KB and NCI-H187. The results showed that uthongine was the best candidate of the series and it exhibited cytotoxicity against a human breast cancer MCF7 line with an IC50 = 3.05 μM.

Keywords: Oxophoebine; cytotoxic activity; oxocrebanine; total syntheses; uthongine.

MeSH terms

  • Alkaloids
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Aporphines / chemical synthesis*
  • Aporphines / chemistry
  • Aporphines / pharmacology*
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Inhibitory Concentration 50
  • KB Cells
  • MCF-7 Cells
  • Microwaves
  • Molecular Structure
  • Stereoisomerism

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Aporphines
  • oxophoebine