title: 2-Aminothiophene-3-carboxylic acid ester derivatives as novel highly selective cytostatic agents.
abstract: 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.
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000, Leuven, Belgium, jan.balzarini@rega.kuleuven.be.
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: J
authors.initials: J
authors.lastname: Thomas
authors.forename: S
authors.initials: S
authors.lastname: Liekens
authors.forename: S
authors.initials: S
authors.lastname: Noppen
authors.forename: W
authors.initials: W
authors.lastname: Dehaen
authors.forename: R
authors.initials: R
authors.lastname: Romagnoli
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D054697:Cytostatic Agents / Q000737:chemistry / Q000627:therapeutic use*; D004952:Esters / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D000596:Amino Acids; D054697:Cytostatic Agents; D004952:Esters; D013876:Thiophenes