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 language | English |
|---|---|
| Pages (from-to) | 90-107 |
| Number of pages | 18 |
| Journal | European Journal of Medicinal Chemistry |
| Volume | 132 |
| DOIs | |
| Publication status | Published - 2017 Jan 1 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
- Drug Discovery
- Organic Chemistry
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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 journal › Article
TY - JOUR
T1 - Using gene expression database to uncover biology functions of 1,4-disubstituted 1,2,3-triazole analogues synthesized via a copper (I)-catalyzed reaction
AU - Su, Chun Li
AU - Tseng, Chia Ling
AU - Ramesh, Chintakunta
AU - Liu, Hsiao-Sheng
AU - Huang, Chi Ying F.
AU - Yao, Ching Fa
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85015814744&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85015814744&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2017.03.034
DO - 10.1016/j.ejmech.2017.03.034
M3 - Article
C2 - 28342400
AN - SCOPUS:85015814744
VL - 132
SP - 90
EP - 107
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
ER -