European Journal of Medicinal Chemistry p. 498 - 510 (2018)
Update date:2022-08-15
Topics:
Li, Peng-Hui
Jiang, Hong
Zhang, Wen-Jin
Li, Yong-Lian
Zhao, Min-Cong
Zhou, Wei
Zhang, Lan-Yue
Tang, Ya-Dong
Dong, Chang-Zhi
Huang, Zhi-Shu
Chen, Hui-Xiong
Du, Zhi-Yun
Novel topoisomerase II (Topo II) inhibitors have gained considerable interest for the development of anticancer agents. In this study, a series of carbazole derivatives containing chalcone analogs (CDCAs) were synthesized and investigated for their Topo II inhibition and cytotoxic activities. The results from Topo II mediated DNA relaxation assay showed that CDCAs could significantly inhibit the activity of Topo II, and the structure-activity relationship indicated the halogen substituent in phenyl ring play an important role in the activity. Further mechanism studies revealed that CDCAs function as non-intercalative Topo II catalytic inhibitors. Moreover, some CDCAs showed micromolar cytotoxic activities. The most potent compound 3h exhibited notable growth inhibition against four human cancer cell lines. Flow cytometric analysis revealed that compounds 3d and 3h arrested the HL-60 cells in sub G1 phase by induction of apoptosis. It was further confirmed by Annexin-V-FITC binding assay. Western blot analysis revealed that compound 3h induces apoptosis likely through the activation of caspase proteins.
View MoreAnhui Gusheng Import&Export CO.,LTD
Contact:86-551-63662296
Address:Jinzhai Road NO.162 ,hefei, china
Zhejiang Rongkai Chemical Technology Co.,Ltd.
Contact:+86-578-8185786
Address:Shangjiang Industrial Zone,Suichang
Dalian Join King Biochemical Tech. Co., Ltd.
Contact:0411 39216206
Address:814 First State Blvd
Contact:+86-27-67841589
Address:Add: 999 Gaoxin Road, Donghu New Technology Development Zone, Wuhan City, Hubei, China
QINGDAO HONG JIN CHEMICAL CO.,LTD.
website:http://www.hongjinchem.com
Contact:+86-532-83657313
Address:2ND Building, 8 Shangqing Road, Qingdao, Shandong Province, China.
Doi:10.1021/acs.oprd.9b00205
(2019)Doi:10.1016/j.tetlet.2007.11.054
(2008)Doi:10.1248/cpb.39.817
(1991)Doi:10.1016/S0040-4039(01)81677-4
(1984)Doi:10.1021/jo00207a055
(1985)Doi:10.1039/b707957e
(2007)