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

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 mu M) and SGC-7901 (IC50 = 2.28 mu M) 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 beta 1 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. (C) 2019 Published by Elsevier Masson SAS.