College of Pharmaceutical Sciences, Zhejiang University, 388 Yuhangtang Road, Hangzhou 310058, PR China.
Eur J Med Chem. 2011 Dec;46(12):5970-7. doi: 10.1016/j.ejmech.2011.10.009. Epub 2011 Oct 13.
Three series of 3-substituted-indolin-2-ones and azaindolin-2-ones have been synthesized and showed potential antiproliferative activity to cancer cell lines. The inhibition activities on VEGF-induced VEGFR phosphorylation were observed for selected 2-indolinones. Among the compounds synthesized, 5-fluoroindolin-2-one derivative 23 with a pyridone unit showed the most significant enzymatic and cellular activities. Flow cytometric analysis indicates that 23 plays a role in suppressing HCT-116 cell proliferation via G1 phase arrest and apoptosis in a dose dependent manner. The binding mode of compound 23 complexed with VEGFR-2 was predicted using FlexX algorithm. Described here are the chemistry and biological testing for these series which will guide the design and optimization of novel 2-indolione antitumor agents.
已经合成了三个系列的 3-取代吲哚啉-2-酮和氮杂吲哚啉-2-酮，并显示出对癌细胞系的潜在抗增殖活性。对所选的 2-吲哚啉酮进行了 VEGF 诱导的 VEGFR 磷酸化抑制活性的观察。在所合成的化合物中，具有吡啶酮单元的 5-氟吲哚啉-2-酮衍生物 23 显示出最显著的酶和细胞活性。流式细胞术分析表明，23 通过 G1 期阻滞和凋亡以剂量依赖的方式在抑制 HCT-116 细胞增殖中发挥作用。使用 FlexX 算法预测了化合物 23 与 VEGFR-2 复合物的结合模式。本文描述了这些系列的化学和生物学测试，这些测试将指导新型 2-吲哚啉酮抗肿瘤药物的设计和优化。
