Semisynthetic analogues of the marine cembranoid sarcophine as prostate and breast cancer migration inhibitors

Bioorg Med Chem. 2011 Aug 15;19(16):4928-34. doi: 10.1016/j.bmc.2011.06.060. Epub 2011 Jun 28.

Abstract

Sarcophine (1) is a bioactive cembranoid diterpene isolated from the Red Sea soft coral Sarcophyton glaucum. Previous semisynthesis attempts resulted in decreased or complete loss of 1's anticancer activity. Sarcophine and analogues showed antimigratory activity against breast and prostate cancer cell lines. This encouraged further semisynthestic optimizations to improve its activity and establish a preliminary structure-activity relationship. Eight new and five known semisynthetic analogues were generated. These compounds were evaluated for their ability to inhibit growth, proliferation, and migration of the prostate and breast metastatic cancer cell lines PC-3 and MDA-MB-231, respectively. Most analogues exhibited enhanced antimigratory activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemistry
  • 4-Butyrolactone / pharmacology
  • 4-Butyrolactone / therapeutic use
  • Animals
  • Anthozoa / chemistry
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Cell Migration Assays
  • Cell Migration Inhibition / drug effects*
  • Cell Proliferation / drug effects*
  • Diterpenes / chemical synthesis
  • Diterpenes / chemistry
  • Diterpenes / pharmacology
  • Diterpenes / therapeutic use
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Indian Ocean
  • Male
  • Prostatic Neoplasms / drug therapy*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Diterpenes
  • sarcophine
  • 4-Butyrolactone