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
N1 - Funding Information:
We are thankful to Professor Chung-Wai Shiau, Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan, for editing the manuscript. Financial support for this work from the National Science Council, Taiwan (NSC 98-2313-B-003-002-MY3 and NSC 101-2313-B-003-002-MY3), the Ministry of Science and Technology, Taiwan (MOST 105–3011-B010-001, MOST 104-2627-B-010-001, and MOST 104-2320-B-003-007), and the National Taiwan Normal University (99T3030-2, 99-D, 100-D-06, and 103-07-C) is gratefully acknowledged.
Publisher Copyright:
© 2017 Elsevier Masson SAS
PY - 2017
Y1 - 2017
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.
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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 - CHIM.THER.
JF - CHIM.THER.
SN - 0223-5234
ER -