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 MoreChangzhou Jiana Chemical Co.,Ltd
website:http://www.jianachem.com
Contact:86-0519-88731808
Address:Zhenglu Town Wujin City, Jiangsu Province
SHANDONG ZHANHUA YONGHAO PHARMACEUTICAL TECH.CO.,LTD
Contact:+86-576-88685096
Address:GENGJU VILLAGE NORTH ONE KILOMETER,ZHANHUA DISTRICT,BINZHOU CITY,SHANDONG PROVINCE,CHINA.
Yingkou Sanzheng Organic Chemical Co. Ltd.
Contact:+86-417-3638818
Address:25 Gengxinli Village, Daqing Road, Yingkou, Liaoning, China
Contact:+86-21-56338808
Address:799 Dunhuang Road, Putuo
Luzhou North Chemical Co., Ltd.
Contact:+86-830-2796784;+86-830-2796776
Address:Gaoba, Longmatan District, Luzhou, Sichuan Province
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)