Antiproliferative activity of novel derivative of thiopyran on breast and colon cancer lines and DNA binding

DNA Cell Biol. 2012 Jan;31(1):128-34. doi: 10.1089/dna.2011.1291. Epub 2011 Jun 28.

Abstract

Dimethyl-5-acetyl-4-methyl-6-(4-methylphenylimino)-6H-thiopyran-2,3-dicarboxylate (4) has been synthesized and its antiproliferative activity is reported here. Compound 4 inhibited the growth of human colon cancer cell line HCT-15 with an IC(50) value of 3.5 μM and of breast cancer cell line MCF-7 with an IC(50) value of 1.5 μM in a dose/time-dependent manner using a sulforhodamine B assay. Moreover, suppression of clonogenic activity occurred after exposure to 4 at a concentration of 4 μM for HCT-15 and 1.7 μM for MCF-7. The results also showed tumor cell invasion through matrigel and cell adhesion. The effect of ligand complexation on DNA structure led to overall affinity constant of K(4-DNA)=9.8×10(4) M(-1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Binding, Competitive
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Collagen / metabolism
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • DNA / chemistry
  • DNA / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Kinetics
  • Laminin / metabolism
  • Models, Chemical
  • Molecular Structure
  • Proteoglycans / metabolism
  • Pyrans / chemical synthesis
  • Pyrans / chemistry
  • Pyrans / metabolism
  • Pyrans / pharmacology*
  • Sulfhydryl Compounds / chemical synthesis
  • Sulfhydryl Compounds / chemistry
  • Sulfhydryl Compounds / metabolism
  • Sulfhydryl Compounds / pharmacology*
  • Time Factors

Substances

  • Antineoplastic Agents
  • Drug Combinations
  • Extracellular Matrix Proteins
  • Laminin
  • Proteoglycans
  • Pyrans
  • Sulfhydryl Compounds
  • dimethyl-5-acetyl-4-methyl-6-(4-methylphenylimino)-6H-thiopyran-2,3-dicarboxylate
  • thiopyran
  • matrigel
  • Collagen
  • DNA