Discovery of novel tricyclic 5H-Pyridazino[4,5-b]indoles as potent antitumor agents: Design, synthesis and biological evaluation

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• 作者：Xin Zhai ; Limei Wang ; Jiyue Shi ; Ping Gong
• 关键词：1 ; Anilino ; 5H ; pyridazino[4 ; 5 ; b]indole ; EGFR inhibitor ; Cytotoxicity
• 刊名：Chemical Research in Chinese Universities
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：31
• 期：3
• 页码：372-380
• 全文大小：589 KB
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• 作者单位：Xin Zhai (1)
  Limei Wang (1)
  Jiyue Shi (1)
  Ping Gong (1)
  
  1. Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China
  
• 刊物主题：Chemistry/Food Science, general; Analytical Chemistry; Inorganic Chemistry; Organic Chemistry; Physical Chemistry;
• 出版者：Springer Berlin Heidelberg
• ISSN：2210-3171

文摘

A novel series of 5H-pyridazino[4,5-b]indoles(L-01—L-32) was synthesized and characterized by means of 1H NMR, MS and elemental analysis. The cytotoxicity of the target compounds against Bel-7402 and HT-1080 cell lines were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. Most of them exhibited moderate to excellent cytotoxicity, and six compounds(L-04, L-06, L-18, L-20, L-21 and L-23) possessed dramatically increased cytotoxicity superior to Gefitinib. Of these initial hits, compound L-21 displayed remarkable cytotoxicity against the tested cell lines with half maximal inhibitory concentration(IC50) values of 4.6 and 2.1 μmol/L, respectively, which was 13.9- to 25.6-fold more potent than positive control.