Chemoenzymatic synthesis and cytotoxicity of oenanthotoxin and analogues

Bioorg Med Chem. 2015 Sep 1;23(17):5595-602. doi: 10.1016/j.bmc.2015.07.031. Epub 2015 Jul 22.

Abstract

We developed a synthetic scheme for the synthesis of naturally occurring (14R)-oenanthotoxin and several analogs. Key-steps of this synthesis were an efficient homo-coupling of alkynes and a chemoenzymatic resolution of racemic oenanthotoxin using novozyme 435 and vinyl acetate. The compounds were screened for their cytotoxic activity using a photometric sulforhodamine B assays and several human tumor cell lines. Oenanthotoxin and many derivatives thereof were cytotoxic to tumor cell lines as well as to non-malignant mouse fibroblasts. The highest activity was determined for human ovarian cancer cells A2780 with EC50 = 3.8 μM.

Keywords: Antitumor; Oenanthotoxin; SRB assay; Water dropwort.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Enediynes / chemical synthesis*
  • Enediynes / chemistry*
  • Fatty Alcohols / chemical synthesis*
  • Fatty Alcohols / chemistry*
  • Humans
  • Molecular Structure

Substances

  • Antineoplastic Agents
  • Enediynes
  • Fatty Alcohols
  • enanthotoxin