Using gene expression database to uncover biology functions of 1,4-disubstituted 1,2,3-triazole analogues synthesized via a copper (I)-catalyzed reaction

Chun Li Su, Chia Ling Tseng, Chintakunta Ramesh, Hsiao Sheng Liu, Chi Ying F. Huang, Ching Fa Yao

Research output: Contribution to journalArticle

13 Citations (Scopus)


We have synthesized bioactive 1,4-disubstituted 1,2,3-triazole analogues containing 2H-1,4-benzoxazin-3-(4H)-one derivatives via 1,3-dipolar cycloaddition in the presence of CuI. All the reactions proceeded smoothly and afforded its desired products in excellent yields. Among these analogues, 3y exhibited a better cytotoxic effect on human hepatocellular carcinoma (HCC) Hep 3B cells and displayed less cytotoxicity on normal human umbilical vein endothelial cells, compared with Sorafenib, a targeted therapy for advanced HCC. 3y also induced stronger apoptosis and autophagy. Addition of curcumin enhanced 3y-induced cytotoxicity by further induction of autophagy. Using gene expression signatures of 3y to query Connectivity Map, a glycogen synthase kinase-3 inhibitor (AR-A014418) was predicted to display similar molecular action of 3y. Experiments further demonstrate that AR-A014418 acted like 3y, and vice versa. Overall, our data suggest the chemotherapeutic potential of 3y on HCC.

Original languageEnglish
Pages (from-to)90-107
Number of pages18
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - 2017 Jan 1



  • 1,4-Disubstituted 1,2,3-triazole analogues
  • Apoptosis
  • Autophagy
  • Connectivity map
  • L1000 gene expression profiling
  • Sorafenib

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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