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

10 Citations (Scopus)

Abstract

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
Volume132
DOIs
Publication statusPublished - 2017 Jan 1

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Triazoles
Cytotoxicity
Gene expression
Copper
Hepatocellular Carcinoma
Autophagy
Databases
Glycogen Synthase Kinase 3
Gene Expression
Curcumin
Cycloaddition
Endothelial cells
Human Umbilical Vein Endothelial Cells
Cycloaddition Reaction
Apoptosis
Derivatives
Transcriptome
Experiments
N-(4-methoxybenzyl)-N'-(5-nitro-1,3-thiazol-2-yl)urea
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Su, Chun Li ; Tseng, Chia Ling ; Ramesh, Chintakunta ; Liu, Hsiao-Sheng ; Huang, Chi Ying F. ; Yao, Ching Fa. / Using gene expression database to uncover biology functions of 1,4-disubstituted 1,2,3-triazole analogues synthesized via a copper (I)-catalyzed reaction. In: European Journal of Medicinal Chemistry. 2017 ; Vol. 132. pp. 90-107.
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Using gene expression database to uncover biology functions of 1,4-disubstituted 1,2,3-triazole analogues synthesized via a copper (I)-catalyzed reaction. / Su, Chun Li; Tseng, Chia Ling; Ramesh, Chintakunta; Liu, Hsiao-Sheng; Huang, Chi Ying F.; Yao, Ching Fa.

In: European Journal of Medicinal Chemistry, Vol. 132, 01.01.2017, p. 90-107.

Research output: Contribution to journalArticle

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