College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
Bioorg Med Chem Lett. 2011 Nov 15;21(22):6829-32. doi: 10.1016/j.bmcl.2011.09.025. Epub 2011 Sep 20.
In an effort to find novel N-arylsulfonylimidazolidinones as highly potent anticancer agent, the structure-activity relationship of ethyl 2-methyl-4-(2-oxo-4-phenylimidazolidin-1-ylsulfonyl)phenylcarbamate was explored through synthesis and evaluation of in vitro cytotoxicity of its analogs against HCT116, A549 and NCL-H460 cancer cell lines. Among the synthesized derivatives, the carbamate analogs (4a-f and 4k-p) exhibited superior cytotoxicity to doxorubicin for all cancer cell lines. The SAR studies of these derivatives confirm that the intact 4-phenyl-l-benzenesulfonylimidazolidinone has a pivotal role as a basic pharmacophore and hydrophobic substitutions only at 2-position of 1-aminobenzenesulfonyl moiety are beneficial for the enhancement of the activity.
为了寻找新型的 N-芳基磺酰基咪唑烷酮作为高效抗癌剂，我们通过合成和评估其类似物对 HCT116、A549 和 NCL-H460 癌细胞系的体外细胞毒性，探索了乙基 2-甲基-4-(2-氧代-4-苯基咪唑烷-1-基磺酰基)苯基氨基甲酸酯的构效关系。在合成的衍生物中，氨基甲酸酯类似物（4a-f 和 4k-p）对所有癌细胞系的细胞毒性均优于多柔比星。这些衍生物的 SAR 研究证实，完整的 4-苯基-1-苯磺酰基咪唑烷酮作为基本药效团具有关键作用，而 1-氨基苯磺酰基部分仅在 2-位进行疏水性取代有利于提高活性。
