53157-47-4Relevant academic research and scientific papers
Synthesis and biological evaluation of novel tetrahydro-β-carboline derivatives as antitumor growth and metastasis agents through inhibiting the transforming growth factor-β signaling pathway
Zheng, Cong,Fang, Yuanzhang,Tong, Weiguang,Li, Guoliang,Wu, Haigang,Zhou, Wenbo,Lin, Qingxiang,Yang, Feifei,Yang, Zhengfeng,Wang, Peng,Peng, Yangrui,Pang, Xiufeng,Yi, Zhengfang,Luo, Jian,Liu, Mingyao,Chen, Yihua
, p. 600 - 612 (2014/03/21)
The transforming growth factor beta (TGFβ) signaling cascade is considered as one of the pivotal oncogenic pathways in most advanced cancers. Inhibition of the TGFβ signaling pathway by specific antagonists, neutralizing antibodies, or small molecules is considered as an effective strategy for the treatment of tumor growth and metastasis. Here we demonstrated the identification of a series of tetrahydro-β-carboline derivatives from virtual screening which potentially inhibit the TGFβ signaling pathway. Optimization of the initial hit compound 2-benzoyl-1,3,4,9-tetrahydro-β- carboline (8a) through substitution at different positions to define the structure-activity relationship resulted in the discovery of potent inhibitors of the TGFβ signaling pathway. Among them, compound 8d, one of the tested compounds, not only showed potent inhibition of lung cancer cell proliferation and migration in vitro but also strongly suppressed growth of lung cancer and breast cancer in vivo.
Optimization of 5-hydroxytryptamines as dual function inhibitors targeting phospholipase A2 and leukotriene A4 hydrolase
Meng, Hu,Liu, Ying,Zhai, Yujing,Lai, Luhua
, p. 160 - 167 (2013/03/13)
Dual function inhibitors targeting phospholipase A2 (PLA 2) and leukotriene A4 hydrolase (LTA4H) may balance the arachidonic acid (AA) metabolic network and be used as new anti-inflammatory drugs. In previous study, we discovered multi-target drugs towards the AA metabolic network, among which a dual-target inhibitor (JMC08-4) for human nonpancreatic secretory phospholipase A2 (hnps-PLA 2) and human leukotriene A4 hydrolase (LTA4H-h) was found. Based on the structure of compound JMC08-4, new dual-target inhibitors were designed assisted by molecular docking. In this report, a series of 5-hydroxytryptamine compounds were synthesized; and most of these title compounds showed more potent inhibitory activity than compound JMC08-4 in the in vitro bioassay against these two enzymes. The best one inhibited hnps-PLA 2 and LTA4H-h with IC50 values of 9.2 ± 0.5 μM and 2.4 ± 1.4 μM, respectively.
