2. Academic Validation
  3. Design and synthesis of pregnenolone/2-cyanoacryloyl conjugates with dual NF-κB inhibitory and anti-proliferative activities

Design and synthesis of pregnenolone/2-cyanoacryloyl conjugates with dual NF-κB inhibitory and anti-proliferative activities

  • Bioorg Med Chem Lett. 2017 Oct 15;27(20):4682-4686. doi: 10.1016/j.bmcl.2017.09.013.
Jia-Li Song 1,  Juan Zhang 2,  Chang-Liang Liu 3,  Chao Liu 4,  Kong-Kai Zhu 1,  Fei-Fei Yang 1,  Xi-Gong Liu 1,  João Paulo Figueiró Longo 2,  Luis Alexandre Muehlmann 2,  Ricardo Bentes Azevedo 5,  Yu-Ying Zhang 6,  Yue-Wei Guo 7,  Cheng-Shi Jiang 8,  Hua Zhang 9
Affiliations

Affiliations

  • 1 School of Biological Science and Technology, University of Jinan, Jinan 250022, China.
  • 2 Faculty of Ceilandia, University of Brasilia, Brasilia 72220275, Brazil; Institute of Biological Sciences, University of Brasília, Brasília 70910900, Brazil.
  • 3 Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
  • 4 Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, Jinan 250100, China.
  • 5 Institute of Biological Sciences, University of Brasília, Brasília 70910900, Brazil.
  • 6 School of Biological Science and Technology, University of Jinan, Jinan 250022, China. Electronic address: yuyingzhang2008@163.com.
  • 7 Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 8 School of Biological Science and Technology, University of Jinan, Jinan 250022, China. Electronic address: jiangchengshi-20@163.com.
  • 9 School of Biological Science and Technology, University of Jinan, Jinan 250022, China. Electronic address: bio_zhangh@ujn.edu.cn.
PMID: 28919340 DOI: 10.1016/j.bmcl.2017.09.013
Abstract

Twenty-five novel pregnenolone/2-cyanoacryloyl conjugates (6-30) were designed and prepared, with the aim of developing novel Anticancer drugs with dual NF-κB inhibitory and anti-proliferative activities. Compounds 22 and 27-30 showed inhibition against TNF-α-induced NF-κB activation in luciferase assay, which was confirmed by Western blotting. Among them, compound 30 showed potent NF-κB inhibitory activity (IC50=2.5μM) and anti-proliferative against MCF-7, A549, H157, and HL-60 cell lines (IC50=6.5-36.2μM). The present study indicated that pregnenolone/2-cyanoacryloyl conjugate I can server asa novel scaffold for developing NF-κB inhibitors and anti-proliferative agents in Cancer chemotherapy.

Keywords

2-Cyanoacryloyl; Anti-proliferative activity; Michael acceptor; NF-κB; Pregnenolone.

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