17952-78-2Relevant academic research and scientific papers
Discovery of tetrahydro-?-carboline derivatives as a new class of phosphodiesterase 4 inhibitors
Abdelwaly, Ahmad,Salama, Ismail,Gomaa, Mohamed S.,Helal, Mohamed A.
, p. 3173 - 3187 (2017/10/06)
Abstract: Phosphodiesterase 4 is the primary enzyme responsible for degradation of the second messenger cAMP in many of the cells releasing proinflammatory mediators. Inhibition of this enzyme could help in the management of various inflammatory conditions such as asthma, chronic obstructive pulmonary disorder, arthritis, and psoriasis. In this study, two novel series of tetrahydro-β-carbolines were designed by combining the pharmacophoric features of both tadalafil and piclamilast. Twenty-two compounds were synthesized and assessed for Phosphodiesterase 4 inhibition, four of them showed superior activity to the reference compound IBMX. Docking studies showed that the prepared compounds interact with the crucial Gln443 with variable interactions with the hydrophobic pocket Q2. This is the first report of tetrahydro-β-carbolines as a scaffold for Phosphodiesterase 4 inhibition. Currently, further optimization of the substituents is carried out to fine-tune the hydrophobic interactions and enhance the potency of this novel series of inhibitors.
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.
