Summary
Cytostatic agents often do not discriminate in their cytostatic potential between different tumor cell types in vitro. In this study, several 2-aminothiophene-3-carboxylic acid ester derivatives were discovered that show an unusual cytostatic selectivity for several T-cell (but not B-cell) lymphoma, prostate cancer, kidney carcinoma and hepatoma cell lines. Their 50 % cytostatic concentrations were generally in the higher nanomolar range and were approximately 20- to 50-fold lower for these tumor cell types than for any other tumor cell line or non-tumorigenic cells. The tumor-selective compounds caused a more preferential suppression of protein synthesis than DNA or RNA synthesis and the prototype compound 3 resulted in an accumulation of prostate cancer cells in the G1 phase of their cell cycle. Compound 3 was also shown to induce apoptosis in prostate cancer cells. The 2-aminothiophene-3-carboxylic acid ester derivatives represent novel candidate cytostatic agents to be further explored for their tumor-selective potential.
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Acknowledgments
We are grateful to Mrs. C. Callebaut for dedicated editorial assistance and to Mrs. Lizette van Berckelaer, Kristien Minner and Ria Van Berwaer for excellent technical assistance. The research was supported by the KU Leuven (GOA 10/14). The study sponsors had no role in the writing of the manuscript nor the decision to submit the manuscript for publication.
Conflicts of interest
JB, SL, JT, WD and RR are co-inventors of a patent application filed in June 2012 on the tumor-selective compounds.
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Balzarini, J., Thomas, J., Liekens, S. et al. 2-aminothiophene-3-carboxylic acid ester derivatives as novel highly selective cytostatic agents. Invest New Drugs 32, 200–210 (2014). https://doi.org/10.1007/s10637-013-9981-4
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DOI: https://doi.org/10.1007/s10637-013-9981-4