Journal of Medicinal Chemistry p. 6626 - 6637 (2013)
Update date:2022-07-30
Topics:
Mathieu, Véronique
Van Den Berge, Emilie
Ceusters, Justine
Konopka, Tomasz
Cops, Antonin
Bruyère, Céline
Pirker, Christine
Berger, Walter
Trieu-Van, Tran
Serteyn, Didier
Kiss, Robert
Robiette, Rapha?l
We designed and synthesized 48 aryl-1H-imidazole derivatives and investigated their in vitro growth inhibitory activity in cancer cell lines known to present various levels of resistance to proapoptotic stimuli. The IC50 in vitro growth inhibitory concentration of these compounds ranged from >100 μM to single digit μM. Among the most active compounds, 2i displayed similar in vitro growth inhibition in cancer cells independent of the cells' levels of resistance to proapoptotic stimuli and was found to be cytostatic in melanoma cell lines. Compound 2i was then tested by the National Cancer Institute Human Tumor Cell Line Anti-Cancer Drug Screen, and the NCI COMPARE algorithm did not reveal any correlation between its growth inhibition profiles with the NCI database compound profiles. The use of transcriptomically characterized melanoma models then enabled us to highlight mitochondrial targeting by 2i. This hypothesis was further confirmed by reactive oxygen production measurement and oxygen consumption analysis.
View MoreHangzhou Maytime Bio-Tech Co.,Ltd.
website:http://www.maytime.com.cn
Contact:+86-571-88925295 88920965
Address:NO.2-1701 Ganghui Central Ningwei Street, Xiaoshan Hangzhou Zhejiang China
Shanghai Yingrui Biopharma Co., Ltd
Contact:021-3358 8661*8003
Address:shanghai
RongCheng Tianyu Technology Co.,Ltd.
Contact:86-631-7519595
Address:220Ping Donghai Road RongChengCity,ShangDong Province China
Hefei TNJ chemical industry co.,ltd
website:https://www.tnjchem.com
Contact:+86-551-65418695
Address:B911 Xincheng Business Center, Qianshan Road, Hefei Anhui China
Shanghai Yuking Water Soluble Material Tech Co., Ltd
Contact:86-21-68286299
Address:4F, 13B, No. 600, South Xinyuan Road 201306, Shanghai, China
Doi:10.1074/jbc.M116.747014
(2016)Doi:10.1002/anie.201912161
(2019)Doi:10.1021/ja01027a061
(1968)Doi:10.1021/j100210a040
(1982)Doi:10.1007/BF00629965
(1994)Doi:10.1007/BF00700009
(1993)