Synthesis and Characterization of Two New Thiophene Acetyl Salicylic Acid Esters and their ortho- and para-effect on Anticancer Activity

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. Method: 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. Result: 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.