Villar R, Encio I, Migliaccio M, Gil M J, Martinez-Merino V
Dpto. de Química, Universidad Pública de Navarra, Campus Arrosadía, 31006 Pamplona, Spain.
Bioorg Med Chem. 2004 Mar 1;12(5):963-8. doi: 10.1016/j.bmc.2003.12.012.
In the search of new compounds with antineoplastic activity, we have analysed the effect of several structural modifications on the nucleus 6-benzo[b]thiophenesulphonamide 1,1-dioxide on its cytotoxic activity on tumour cells. Lipophilic substituents on the sulphonamide group significantly increased the cytotoxic activity measured using a panel of human tumour cell lines. Only slight variations on cytotoxicity were obtained when the sulphonamide group occupied the position 5 of the system. The most active compound was the N-4-methoxyphenyl derivative 15, which showed GI(50) values of 1-9 nM against HT-29, CCRF-CEM, K-562 and MEL-AC cells and of 200 nM against HTB-54 cells. Free access to the 3-position of the heterocyclic system seems to be required to obtain cytotoxic derivatives. Derivative 15 was also active at the same level of commercial Doxorubicine against cultured normal human lung fibroblasts.
在寻找具有抗肿瘤活性的新化合物过程中，我们分析了对6-苯并[b]噻吩磺酰胺1,1-二氧化物核进行的几种结构修饰对其对肿瘤细胞的细胞毒性活性的影响。磺酰胺基团上的亲脂性取代基显著提高了使用一组人类肿瘤细胞系测得的细胞毒性活性。当磺酰胺基团占据该体系的5位时，细胞毒性仅有轻微变化。活性最高的化合物是N-4-甲氧基苯基衍生物15，其对HT-29、CCRF-CEM、K-562和MEL-AC细胞的GI(50)值为1 - 9 nM，对HTB-54细胞的GI(50)值为200 nM。似乎需要杂环体系的3位能够自由接入才能获得具有细胞毒性的衍生物。衍生物15对培养的正常人肺成纤维细胞的活性与市售阿霉素处于同一水平。
