title: Synthesis and Characterization of Two New Thiophene Acetyl Salicylic Acid Esters and their ortho- and para-effect on Anticancer Activity.
abstract: OBJECTIVE
  The present study aimed to explore the cytotoxic effect of ortho- and para-positional isomers of thiophene acetyl salicylic acid esters against cancer and normal cell lines.
  
  
  METHODS
  Two new thiophene-2-acetic acid esters (2-((2-(thiophen-2-yl)acetyl)thio)benzoic acid and 4-((2-(thiophen-2- yl)acetyl)thio)benzoic acid) were synthesized and characterized by Elemental analysis, Fourier transform infrared spectroscopy, 1H-nuclear magnetic resonance (NMR), 13C-NMR and High-resolution mass spectroscopy. The compounds were tested for their in vitro cytotoxic activity against A549 and Caco2 tumor cell lines and CCD- 19Lu and CCD 841 CoN normal cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,4,diphenyltetrazolium bromide assay. 2-((2-(thiophene-2-yl)acetyl)thio)benzoic acid showed a higher activity with (IC50 = 239.88µM/mL) compared with a reference drug nearly as active as cyclophosphamide (IC50 = 257.11 µM/mL) on Caco2 cell line. Apoptosis was observed by flow cytometric analysis on Caco2 cells.
  
  
  RESULTS
  Thus, positional isomerism is critical for the pharmacological properties of thiophene acetyl salicylic acid esters against colon cancer cell line compared with nonsmall cell lung cancer cell line. The ortho-isomer induced cell death and was much more potent than the para-isomer.
authors.affiliation: Chemistry Department, Faculty of Science, Anadolu University, 26470, Eskisehir. Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Unver
authors.affiliation: Pharmaceutical Microbiology Department, Faculty of Pharmacy, Anadolu University, 26470, Eskisehir. Turkey.
authors.forename: Zerrin
authors.initials: Z
authors.lastname: Canturk
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D020156:Salicylic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004952:Esters; D013876:Thiophenes; D020156:Salicylic Acid
keywords: A549; Caco2; MTT; anticancer activity; cancer; thiophene acetic acid ester