Five new phorbol esters with cytotoxic and selective anti-inflammatory activities from Croton tiglium

Bioorg Med Chem Lett. 2015 May 1;25(9):1986-9. doi: 10.1016/j.bmcl.2015.03.017. Epub 2015 Mar 14.

Abstract

Five new phorbol esters, (four phorbol diesters, 1-4, and one 4-deoxy-4α-phorbol diester, 5), as well as four known phorbol esters analogues (6-9) were isolated and identified from the branches and leaves of Croton tiglium. Their structures were elucidated mainly by extensive NMR spectroscopic, and mass spectrometric analysis. Among them, compound (1) was the first example of a naturally occurring phorbol ester with the 20-aldehyde group. Compounds 2-5, and 7-9 showed potent cytotoxicity against the K562, A549, DU145, H1975, MCF-7, U937, SGC-7901, HL60, Hela, and MOLT-4 cell lines, with IC50 values ranging from 1.0 to 43 μM, while none of the compounds exhibited cytotoxic effects on normal human cell lines 293T and LX-2, respectively. In addition, compound 3 exhibited moderate COX-1 and COX-2 inhibition, with IC50 values of 0.14 and 8.5 μM, respectively.

Keywords: Anti-inflammatory activity; Croton tiglium; Cytotoxicity; Phorbol esters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Croton / chemistry*
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase Inhibitors / chemistry
  • Cyclooxygenase Inhibitors / isolation & purification
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Phorbol Esters / chemistry
  • Phorbol Esters / isolation & purification
  • Phorbol Esters / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Phorbol Esters
  • Cyclooxygenase 1
  • Cyclooxygenase 2