International Journal of Molecular Sciences (2021)
Update date:2022-08-04
Topics:
Cie?lak, Marcin
Napiórkowska, Mariola
Ka?mierczak‐barańska, Julia
Królewska‐golińska, Karolina
Hawry?, Anna
Wybrańska, Iwona
Nawrot, Barbara
Based on previously identified dicarboximides with significant anticancer and immunomodulatory activities, a series of 26 new derivatives were designed and synthesized by the Diels–Alder reaction between appropriate diene and maleimide or hydroxymaleimide moieties. The resulting imides were functionalized with alkanolamine or alkylamine side chains and subsequently converted to their hydrochlorides. The structures of the obtained compounds were confirmed by 1H and 13C NMR and by ESI MS spectral analysis. Their cytotoxicity was evaluated in human leukemia (K562, MOLT4), cervical cancer (HeLa), and normal endothelial cells (HUVEC). The majority of derivatives exhibited high to moderate cytotoxicity and induced apoptosis in K562 cells. Microarray gene profiling demonstrated upregulation of proapoptotic genes involved in receptor‐mediated and mitochondrial cell death pathways as well as antiapoptotic genes involved in NF‐kB signaling. Selected dicarboximides activated JNK and p38 kinases in leukemia cells, suggesting that MAPKs may be involved in the regulation of apoptosis. The tested dicarboximides bind to DNA as assessed by a plasmid DNA cleavage protection assay. The selected dicarboximides offer new scaffolds for further development as anticancer drugs.
View MoreJinan Yufeng Bioengineering Co., Ltd.
Contact:+86-531-83130545/83130528/83130525/83130505
Address:Rm415,Building2,No19,Huaneng Road,Jinan, Shandong, China
Shanghai Sinofluoro Scientific Co., Ltd
Contact:+86-21-64279360
Address:Room 1006,Building 3,#58 East Xinjian Road, Shanghai ,201100,China,
Cangzhou Bao Lai Da Import&Export Trading Co.,Ltd
Contact:86-317-2096605
Address:Cangzhou City,HeBei Province,China
Contact:86-10-62664360
Address:Building 10,No.18 AnNingZhuang East Road, GuangHua Pioneer Park,HaiDian District, BeiJing China
Baoding City Light Industry And Textiles Imp.& Exp. Corp. Chemical Department.
Contact:86-312-3262436
Address:NO.658 CHAOYANG SOUTH STREET,BAODING CITY HEBEI CHINA
Doi:10.1021/jo9721195
(1998)Doi:10.1016/j.tetlet.2014.01.010
(2014)Doi:10.1021/jo402658h
(2014)Doi:10.1002/hc.10129
(2003)Doi:10.1021/om00031a009
(1993)Doi:10.3762/bjoc.14.92
(2018)