Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000, Leuven, Belgium,
Invest New Drugs. 2014 Feb;32(1):200-10. doi: 10.1007/s10637-013-9981-4. Epub 2013 Jun 4.
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.
细胞抑制剂在体外通常不能区分不同肿瘤细胞类型的细胞抑制潜力。在这项研究中，发现了几种 2-氨基噻吩-3-羧酸酯衍生物，它们对几种 T 细胞（而非 B 细胞）淋巴瘤、前列腺癌、肾癌细胞和肝癌细胞系具有异常的细胞抑制选择性。它们的 50%细胞抑制浓度通常在较高的纳摩尔范围内，对于这些肿瘤细胞类型，其浓度比任何其他肿瘤细胞系或非肿瘤细胞低 20 至 50 倍。这些肿瘤选择性化合物导致蛋白质合成的抑制比 DNA 或 RNA 合成更具选择性，原型化合物 3 导致前列腺癌细胞在细胞周期的 G1 期积累。化合物 3 还被证明可诱导前列腺癌细胞凋亡。2-氨基噻吩-3-羧酸酯衍生物代表新型候选细胞抑制剂，可进一步探索其肿瘤选择性潜力。
