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

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).

• Authors: Mehdi Rajabi, Mohammad A Khalilzadeh, Jamshid Mehrzad
• Journal: DNA and cell biology (DNA Cell Biol) Vol. 31 Issue 1 Pg. 128-34 (Jan 2012) ISSN: 1557-7430 [Electronic] United States
• PMID: 21711159 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• Antineoplastic Agents (chemical synthesis, metabolism, pharmacology)
• Binding, Competitive
• Breast Neoplasms (metabolism, 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, pathology)
• DNA (chemistry, 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, chemistry, metabolism, pharmacology)
• Sulfhydryl Compounds (chemical synthesis, chemistry, metabolism, pharmacology)
• Time Factors