Synthesis and antitumour evaluation of peptidyl-like derivatives containing the 1,3-benzodioxole system

Eur J Med Chem. 2007 Mar;42(3):351-7. doi: 10.1016/j.ejmech.2006.10.007. Epub 2006 Dec 18.

Abstract

In the scope of a research program aiming at the synthesis and pharmacological evaluation of novel possible antitumour prototype compounds, we described in this paper the synthesis of peptidyl-like derivatives containing the 1,3-benzodioxole system. The proliferation inhibitors tested against tumour cell lines identified the derivatives tyrosine (4f) and lysine (4 g) as the most active among them, presenting IC(50) values in micromolar range and are more active than Safrole. For the study on the embryonic development, Safrole did not show any selectivity in this latter assay, which indicates that Safrole acts as a 'cell cycle-nonspecific' inhibitory agent. However, compound 4f presented a fair antimitotic effect, mainly on third cleavage and blastulae stages (38% and 1.7% of normal development, at 10 microg/mL), suggesting a time-dependent activity and a 'cell cycle-specific' agent action. Neither derivatives revealed hemolytic action in assay with mouse erythrocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Dioxoles / chemical synthesis*
  • Dioxoles / pharmacology*
  • Drug Screening Assays, Antitumor
  • Embryo, Nonmammalian / drug effects
  • Embryonic Development / drug effects
  • Hemolysis / drug effects
  • Humans
  • In Vitro Techniques
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Mice
  • Sea Urchins
  • Spectrophotometry, Infrared
  • Tetrazolium Salts
  • Thiazoles

Substances

  • Antineoplastic Agents
  • Dioxoles
  • Indicators and Reagents
  • Tetrazolium Salts
  • Thiazoles
  • thiazolyl blue
  • 1,3-benzodioxole