Synthesis of novel α-santonin derivatives as potential cytotoxic agents

Eur J Med Chem. 2010 Dec;45(12):6045-51. doi: 10.1016/j.ejmech.2010.10.003. Epub 2010 Oct 23.

Abstract

Ten novel α-santonin derivatives have been synthesized as cytotoxic agents. The in vitro antitumor activity of these compounds has been evaluated against cancer cells lines. Structure-activity relationships indicate that α-methylene-γ-lactone and endoperoxide functionalities play important roles in conferring cytotoxicity. The compounds 2-4, possessing the α-methylene-γ-lactone group showed IC50 values between 5.70 and 16.40 μM. Mixture of isomers 5 and 6, with the α-methylene-γ-lactone and endoperoxide functionalities, displayed the greatest activity, with IC50 values between 1.45 and 4.35 μM. The biological assays conducted with normal cells revealed that the compounds 2, 5 and 6 are selective against cancer cells lines tested. Bioactive lactones described herein and in our previous report did not cause disruption of the cell membrane in mouse erythrocytes.

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
  • Drug Screening Assays, Antitumor
  • HL-60 Cells
  • Humans
  • Molecular Structure
  • Santonin / analogs & derivatives
  • Santonin / chemical synthesis*
  • Santonin / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Santonin