Biocatalytic and semisynthetic optimization of the anti-invasive tobacco (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol

Bioorg Med Chem. 2008 Mar 15;16(6):2886-93. doi: 10.1016/j.bmc.2007.12.056. Epub 2008 Jan 3.

Abstract

Tobacco cembranoids were reported to inhibit tumorigenesis. Biocatalysis of (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (1) using the symbiotic Bacillus sp. NC5, Bacillus sp. NK8, and Bacillus sp. NK7, isolated from the Red Sea sponge Negombata magnifica, afforded two new and four known hydroxylated metabolites 3-8. The use of symbiotic marine bacteria as biocatalysts for bioactive natural product scaffolds is very rare. Cembranoid 1 carbamate analogs 9-11 were prepared by its reaction with corresponding isocyanates. Cembranoid 1 and its bioconversion and carabamate products show anti-invasive activity against the human highly metastatic prostate PC-3M cancer cell line at 10-50 nM doses in Matrigel assay.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Bacillus / metabolism*
  • Cell Line, Tumor
  • Diterpenes / chemistry*
  • Diterpenes / pharmacology*
  • Drug Screening Assays, Antitumor
  • Humans
  • Male
  • Neoplasm Invasiveness / prevention & control*
  • Nicotiana / chemistry
  • Porifera / microbiology
  • Prostatic Neoplasms / drug therapy*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Diterpenes