European Journal of Medicinal Chemistry p. 1395 - 1405 (2018)
Update date:2022-08-03
Topics:
Zhu, Min
Wang, Jiabing
Xie, Jingwen
Chen, Liping
Wei, Xiaoyan
Jiang, Xing
Bao, Miao
Qiu, Yanyi
Chen, Qian
Li, Wulan
Jiang, Chengxi
Zhou, Xiaoou
Jiang, Liping
Qiu, Peihong
Wu, Jianzhang
Chalcone, a natural structure, demonstrates many pharmacological activities including anticancer, and one promising mechanism is to modulate the generation of ROS. It has been known that pyroptosis is associated with anticancer effects, whereas there is fewer researches about ROS-mediated pyroptosis triggered by chemotherapy drugs. Moreover, incorporation of a α,β-unsaturated ketone unit into chalcone may be an effective strategy for development of chemotherapy drugs. Hence, a number of chalcone analogues bearing a α,β-unsaturated ketone were synthesized from chalcone analogues 1 with modest anticancer activities as the lead compound. Structure-activity relationship (SAR) studies confirmed the function of α,β-unsaturated ketone to improve anticancer activity. Notably, compound 8, bearing a α,β-unsaturated ketone, is the most potent inhibitor of cancer, with IC50 values on NCI-H460, A549 and H1975 cells of 2.3 ± 0.3, 3.2 ± 0.0 and 5.7 ± 1.4 μM, respectively. Besides, 8 showed antiproliferative ability against NCI-H460 cells in a time- and concentration-dependent manner through modulating ROS to induce caspase-3-mediated pyroptosis, and displayed a better safety profile in vivo. Overall, these results demonstrated that compound 8 is a candidate agent and a potential lead compound for development of chemotherapy drugs, and can be used as a probe to further examine the mechanism of ROS-dependent pyroptosis.
View MoreContact:+86-571-86217390
Address:No.567 Dengcai Street,Sandun,Westlake District,Hangzhou310030,Zhejiang,China.
Shanghai Hongbang Medical Technology CO.,. Ltd
Contact:13671516988 /18917636693
Address:Room1, No67 Building, Yongde Road369, Wujing Town, Minhang Districy, Shanghai CIty, China.
ShangHai Soyoung Biotechnology Inc
website:http://www.soyoungbio.com
Contact:+86-21-69893009
Address:shanghai
Hangzhou GreenCo Science & Technology Co., Ltd.
Contact:86-571-88257303
Address:1713 Room,Jingui Building,Gudun Road,Xihu District,Hangzhou,China
Jinan Decheng Hemu Medical Technology Co.,Ltd.
Contact:+86-531-68650525
Address:NO.554 Zhengfeng Road High-new Technology Development Zone
Doi:10.3987/com-07-s(w)16
(2007)Doi:10.1021/ol702989g
(2008)Doi:10.1016/j.tetasy.2007.11.041
(2008)Doi:10.1016/j.bmcl.2007.12.024
(2008)Doi:10.1021/ja0767579
(2008)Doi:10.1021/jo01362a018
(1957)