Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China; Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China.
College of Sciences, Tianjin University of Science and Technology, Tianjin 300457, PR China.
Bioorg Med Chem Lett. 2014 Jan 15;24(2):591-4. doi: 10.1016/j.bmcl.2013.12.001. Epub 2013 Dec 8.
Forty four di- or trisubstituted novel isatin derivatives were designed and synthesized in 5-6 steps in 25-45% overall yields. Their structures were confirmed by (1)H NMR and (13)C NMR as well as LC-MS. The anticancer activity of these new isatin derivatives against three human tumor cell lines, K562, HepG2 and HT-29, were evaluated by MTT assay in vitro. SAR studies suggested that the combination of 1-benzyl and 5-[trans-2-(methoxycarbonyl)ethen-1-yl] substitution greatly enhance their cytotoxic activity, whereas an intact carbonyl functionality on C-3 as present in the parent ring is required to such a potency. This study leads to the identification of two highly active molecules, compounds 2h (IC50=3 nM) and 2k (IC50=6 nM), against human leukemia K562 cells.
设计并合成了 44 个二取代或三取代新型色胺衍生物，总收率为 25-45%，经 5-6 步反应得到。通过 1H NMR 和 13C NMR 以及 LC-MS 对其结构进行了确证。采用 MTT 法体外评价了这些新的色胺衍生物对三种人肿瘤细胞系（K562、HepG2 和 HT-29）的抗癌活性。SAR 研究表明，1-苄基和 5-[反式-2-（甲氧羰基）乙烯基]取代的组合极大地增强了它们的细胞毒性活性，而在母体环中存在完整的 C-3 羰基官能团对于这种活性是必需的。本研究鉴定了两种对人白血病 K562 细胞具有高活性的分子，化合物 2h（IC50=3 nM）和 2k（IC50=6 nM）。
