Mimicry of annonaceous acetogenins: enantioselective synthesis of a (4R)-hydroxy analogue having potent antitumor activity

J Org Chem. 2002 May 17;67(10):3404-8. doi: 10.1021/jo016396u.

Abstract

The (4R)-hydroxylated analogues of annonaceous acetogenin mimicking compound 2 were designed and synthesized structurally on the basis of the naturally occurring annonaceous acetogenin bullatacin, which was discovered as a typical member of the novel family of polyketides with potent cytotoxicity, antitumoral, and other biological activities. The preliminary screenings show that the IC(50) values of 2 were 1.6 x 10(-3) and 8 x 10(-2) microg/mL against HT-29 and HCT-8, respectively. A remarkable enhancement effect was observed by the activity comparison of 1c and its (4R)-hydroxylated analogue 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annonaceae / chemistry*
  • Antineoplastic Agents, Phytogenic* / chemical synthesis
  • Antineoplastic Agents, Phytogenic* / chemistry
  • Antineoplastic Agents, Phytogenic* / pharmacology
  • Cells, Cultured / drug effects
  • Colonic Neoplasms
  • Dose-Response Relationship, Drug
  • Doxorubicin / pharmacology
  • Drug Screening Assays, Antitumor
  • Furans* / chemical synthesis*
  • Furans* / chemistry
  • Furans* / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Intestines
  • Molecular Mimicry
  • Molecular Structure
  • Stereoisomerism
  • Tumor Cells, Cultured / drug effects

Substances

  • 3-((2R,13S)-2,13-dihydroxy-14-(2-(2S)-hydroxydodecyloxy)ethoxy)tetradecyl-5-methyl-5H-furan-2-one
  • Antineoplastic Agents, Phytogenic
  • Furans
  • bullatacin
  • Doxorubicin