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.
|Number of pages||18|
|Journal||European Journal of Medicinal Chemistry|
|Publication status||Published - 2017|
- 1,4-Disubstituted 1,2,3-triazole analogues
- Connectivity map
- L1000 gene expression profiling
ASJC Scopus subject areas
- Drug Discovery
- Organic Chemistry
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CCDC 871251: Experimental Crystal Structure Determination
Su, C. (Creator), Tseng, C. (Creator), Ramesh, C. (Creator), Liu, H. (Creator), Huang, C. F. (Creator) & Yao, C. (Creator), Unknown Publisher, 2017
DOI: 10.5517/ccdc.csd.ccy7lwm, http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.ccy7lwm&sid=DataCite