Role of the phenolic hydroxyl group in the biological activities of simplified analogue of aplysiatoxin with antiproliferative activity

Bioorg Med Chem Lett. 2010 Oct 15;20(20):6064-6. doi: 10.1016/j.bmcl.2010.08.051. Epub 2010 Aug 13.

Abstract

The 18-deoxy derivative (3) of a simplified analogue (1) of aplysiatoxin with antiproliferative activity was synthesized to examine the role of the phenolic hydroxyl group at position 18 in the biological activities of 1. Compound 3 as well as 1 showed significant affinity for protein kinase Cδ (PKCδ), and the antiproliferative activity of 3 was slightly higher than that of 1. However, the anti-tumor-promoting activity of 3 was less than that of 1 in vitro, suggesting that the phenolic hydroxyl group of 1 is necessary for the anti-tumor-promoting activity but not for the binding of PKCδ and antiproliferative activity. Moreover, PKC isozyme selectivity of 3 was similar to that of 1, suggesting non-PKC receptors for these compounds to play some roles in the anti-tumor-promoting activity of 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Hydroxyl Radical / chemical synthesis
  • Hydroxyl Radical / chemistry*
  • Hydroxyl Radical / pharmacology*
  • Lyngbya Toxins / chemical synthesis
  • Lyngbya Toxins / chemistry*
  • Lyngbya Toxins / pharmacology*
  • Neoplasms / drug therapy
  • Protein Kinase C / metabolism

Substances

  • Antineoplastic Agents
  • Lyngbya Toxins
  • Hydroxyl Radical
  • aplysiatoxin
  • Protein Kinase C