New synthesis of two tridentate bipyrazolic compounds and their cytotoxic activity tumor cell lines

Nat Prod Res. 2007 Sep;21(11):947-52. doi: 10.1080/14786410701371314.

Abstract

Two new tripodal compounds - 4-{bis[(3,5-dimethyl-1H-pyrazole-1-yl)methyl]amino}butane-1-ol (1); ethyl 1-[((2-hydroxyethyl){[3-(ethoxycarbonyl)-5-methyl-1H-pyrazole-1-yl]methyl} amino)methyl]-5-methyl-1H-pyrazole-3-carboxylate (2) were reported. The evaluation of the cytotoxic properties in vitro of these ligands, was examined on two tumor cell lines - P815 (mastocytome murine) and Hep (carcinoma of human larynx). The concentration required to induce 50% of lysis (IC(50)) was more pronounced against P815 cell line (IC(50): 39.42 microg mL(-1) for the compound 1 and 97.74 microg mL(-1) for the compound 2) than the Hep cell line (IC(50): 83.49 microg mL(-1) for compound 1 and 185.30 microg mL(-1) for compound 2). Statistical analysis shows that the compound 1 is two to three folds more cytotoxic than the compound 2 (p < 0.05). Interestingly, the cytotoxic activity depends strongly on both the substituents linked to the aminic nitrogen and pyrazolic rings.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Structure-Activity Relationship

Substances

  • 4-(bis((3,5-dimethyl-1H-pyrazole-1-yl)methyl)amino)butane-1-ol
  • Antineoplastic Agents
  • Pyrazoles
  • ethyl-1-(((2-hydroxyethyl)((3-(ethoxycarbonyl)-5-methyl-1H-pyrazole-1-yl)methyl)amino)methyl)-5-methyl-1H-pyrazole-3-carboxylate