2. Academic Validation
  3. Design and synthesis of new triazoles linked to xanthotoxin for potent and highly selective anti-gastric cancer agents

Design and synthesis of new triazoles linked to xanthotoxin for potent and highly selective anti-gastric cancer agents

  • Bioorg Med Chem Lett. 2017 Nov 1;27(21):4871-4875. doi: 10.1016/j.bmcl.2017.09.040.
Qing-Kun Shen 1,  Chuan-Feng Liu 1,  Hong-Jian Zhang 1,  Yu-Shun Tian 2,  Zhe-Shan Quan 3
Affiliations

Affiliations

  • 1 Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, China.
  • 2 Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, China. Electronic address: ystian@ybu.edu.cn.
  • 3 Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin 133002, China. Electronic address: zsquan@ybu.edu.cn.
PMID: 28947149 DOI: 10.1016/j.bmcl.2017.09.040
Abstract

Two series of xanthotoxin-triazole derivatives were designed, synthesized, and studied for their antiproliferative properties. The in vitro cytotoxicity of the compounds in the AGS Cancer cell line and the L02 normal cell line was evaluated via MTT assay. Among the synthesized compounds, 9-((1-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methoxy)-7H-furo[3,2-g]chromen-7-one (6p) was found to have the greatest antiproliferative activity against AGS cells (IC50=7.5μM) and showed better activity than the lead compound (xanthotoxin, IC50>100μM) and the reference drug (5-fluorouracil, IC50=29.6μM) did. The IC50 value of 6p in L02 cells was 13.3 times higher than that in the AGS cells. Therefore, the compound exhibited better therapeutic activity and specificity compared with the positive control 5-fluorouracil. Cell cycle analysis revealed that compound 6p inhibited cell growth via the induction of S/G2 phase arrest in AGS cells. Compound 6p was identified as a promising lead compound for the further development and identification of 1,2,3-triazole-based Anticancer agents.

Keywords

AGS cells; Antiproliferation; Triazole; Xanthotoxin.

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