Synthesis and biological evaluation of novel 1-O- and 14-O-derivatives of oridonin as potential anticancer drug candidates

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4741-4. doi: 10.1016/j.bmcl.2008.06.097. Epub 2008 Jul 3.

Abstract

Novel 1-O- and 14-O-derivatives of oridonin were synthesized and biologically evaluated. All of the derivatives exhibited stronger cytotoxicity against six cancer cell lines (BGC-7901, SW-480, HL-60, BEL-7402, A549, and B16) than oridonin in vitro, and some of them were more potent than oridonin and cyclophosphamide in vivo. Compounds Ib and IIg were the most potent with the IC(50) values of 0.84 microM for Ib in HL-60 cell and 1.00 microM for IIg in BEL-7402 cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical / methods
  • Diterpenes, Kaurane / chemistry*
  • Diterpenes, Kaurane / isolation & purification*
  • Drug Design
  • Drug Screening Assays, Antitumor*
  • Fluorouracil / chemical synthesis
  • Fluorouracil / pharmacology
  • HL-60 Cells
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Models, Chemical
  • Structure-Activity Relationship
  • Tetrazolium Salts / pharmacology
  • Thiazoles / pharmacology

Substances

  • Antineoplastic Agents
  • Diterpenes, Kaurane
  • Tetrazolium Salts
  • Thiazoles
  • oridonin
  • thiazolyl blue
  • Fluorouracil