Synthesis and biological evaluation of 2-indolinone derivatives as potential antitumor agents.
Synthesis and biological evaluation of 2-indolinone derivatives as potential antitumor agents.
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DOI：
10.1016/j.ejmech.2011.10.009
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发表时间：
2011-12
影响因子：
6.7
通讯作者：
H. Zou;Liang Zhang;Jingfeng Ouyang;M. Giulianotti;Yongping Yu
中科院分区：
文献类型：
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作者：
H. Zou;Liang Zhang;Jingfeng Ouyang;M. Giulianotti;Yongping Yu
合成了三个系列的3-取代吲哚啉-2-酮和氮杂吲哚啉-2-酮，并显示出潜在的抗肿瘤细胞增殖活性。选择2-吲哚啉酮类化合物对VEGF诱导的VEGFR磷酸化具有抑制活性。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显示出最显著的酶活性和细胞活性。流式细胞仪分析表明，23通过G1期阻滞和凋亡以剂量依赖性方式抑制HCT-116细胞增殖。使用FlexX算法预测化合物23与VEGFR-2复合的结合模式。本文介绍了这些系列化合物的化学和生物学测试，这些测试将指导新型2-吲哚酮抗肿瘤药物的设计和优化。
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.