Department of Biology, Hobart and William Smith Colleges, Geneva, NY 14456, USA.
Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA.
Bioorg Med Chem Lett. 2021 Jun 1;41:127991. doi: 10.1016/j.bmcl.2021.127991. Epub 2021 Mar 26.
Analogs of diarylpyrrolinone lead compound 1 were prepared and tested for anti-proliferative activity in U-937 cancer cells. Alterations of 1 focused on modifying the two nitrogen atoms: a) the pyrrolinone nitrogen atom was substituted with a propyl group or replaced with an oxygen atom (furanone), and b) the substituents on the indole nitrogen were varied. These changes led to the discovery of a furanone analog 3b with sub-micromolar anti-cancer potency and tubulin polymerization inhibition activity.
二芳基吡咯啉酮先导化合物 1 的类似物被制备出来，并在 U-937 癌细胞中进行了抗增殖活性测试。对 1 的改造集中在修饰两个氮原子上：a）吡咯烷酮氮原子被丙基取代或被氧原子（呋喃酮）取代，b）吲哚氮上的取代基发生变化。这些变化导致发现了具有亚微米抗癌效力和微管蛋白聚合抑制活性的呋喃酮类似物 3b。
