2. Academic Validation
  3. Synthesis and anti-gastric cancer activity evaluation of novel triazole nucleobase analogues containing steroidal/coumarin/quinoline moieties

Synthesis and anti-gastric cancer activity evaluation of novel triazole nucleobase analogues containing steroidal/coumarin/quinoline moieties

  • Eur J Med Chem. 2019 Nov 1:181:111520. doi: 10.1016/j.ejmech.2019.07.023.
Jian-Wei Zhao 1,  Zeng-Hui Wu 2,  Jia-Wen Guo 1,  Ming-Jie Huang 1,  Ya-Zhen You 1,  Hong-Min Liu 3,  Li-Hua Huang 4
Affiliations

Affiliations

  • 1 College of Chemistry and Molecular Engineering, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, PR China.
  • 2 Luoyang Center for Disease Control and Prevention, 9 Zhenghe Road, Luoyang, Henan, 471023, PR China.
  • 3 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, PR China. Electronic address: liuhm@zzu.edu.cn.
  • 4 College of Chemistry and Molecular Engineering, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, PR China. Electronic address: hlh606@zzu.edu.cn.
PMID: 31404863 DOI: 10.1016/j.ejmech.2019.07.023
Abstract

A series of novel triazole nucleobase analogues containing steroidal/coumarin/quinoline moieties have been synthesized based on copper-catalyzed azide-alkyne cycloaddition (CuAAC). The anti-cancer activity of the new triazole nucleobase analogues was studied in gastric Cancer cell lines (MGC-803, SGC-7901) and normal gastric epithelial cells (GES-1) in vitro. Some of the synthesized compounds could significantly inhibit the proliferation of these tested Cancer cells. Among the tested compounds, compound 20c demonstrated good anti-proliferation activity against MGC-803 cells (IC50 = 1.48 μM) and SGC-7901 (IC50 = 2.28 μM) cells as well as the best selectivity between the Cancer and normal cells. Further mechanistic studies indicated that compound 20c could down-regulate the expression of TGF β1 both in the tested gastric Cancer cell lines and inhibit the cell migration and invasion. The results of the study indicate that compound 20c could be used as a promising skeleton for anti-gastric Cancer agents with improved efficacy and less side effects.

Keywords

1,2,3-Triazole; Anti-cancer activity; Hybrid; Invasion; Migration; Nucleobase.

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