title: 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.affiliation: Department of Chemistry and Biochemistry, Islamic Azad University, Neyshabur Branch, Neyshabur, Iran. m.rajabi.s@gmail.com
authors.forename: Mehdi
authors.initials: M
authors.lastname: Rajabi
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Khalilzadeh
authors.forename: Jamshid
authors.initials: J
authors.lastname: Mehrzad
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D007797:Laminin / Q000378:metabolism; D008956:Models, Chemical; D015394:Molecular Structure; D011509:Proteoglycans / Q000378:metabolism; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D016326:Extracellular Matrix Proteins; D007797:Laminin; D011509:Proteoglycans; D011714:Pyrans; D013438:Sulfhydryl Compounds; C570749:dimethyl-5-acetyl-4-methyl-6-(4-methylphenylimino)-6H-thiopyran-2,3-dicarboxylate; C522033:thiopyran; C059485:matrigel; D003094:Collagen; D004247:DNA