Molecules (2020)
Update date:2022-07-29
Topics:
Balboni, Elisa
Brancale, Andrea
Estévez, Francisco
Estévez-Sarmiento, Francisco
Ferla, Salvatore
Hamel, Ernest
Manfredini, Stefano
Oliva, Paola
Onnis, Valentina
Quintana, José
Romagnoli, Romeo
Induction of apoptosis is a common chemotherapeutic mechanism to kill cancer cells The thiazole system has been reported over the past decades as a building block for the preparation of anticancer agents. A novel series of 2-arylalkylamino-4-amino-5-(3′,4′,5′-trimethoxybenzoyl)-thiazole derivatives designed as dual inhibitors of tubulin and cyclin-dependent kinases (CDKs) were synthesized and evaluated for their antiproliferative activity in vitro against two cancer cell lines and, for selected highly active compounds, for interactions with tubulin and cyclin-dependent kinases and for cell cycle and apoptosis effects. Structure-activity relationships were elucidated for various substituents at the 2-position of the thiazole skeleton. Among the synthesized compounds, the most active analogues were found to be the p-chlorobenzylamino derivative 8e as well as the p-chloro and p-methoxyphenethylamino analogues 8f and 8k, respectively, which inhibited the growth of U-937 and SK-MEL-1 cancer cell lines with IC50 values ranging from 5.7 to 12.2 μM. On U-937 cells, the tested compounds 8f and 8k induced apoptosis in a time and concentration dependent manner. These two latter molecules did not affect tubulin polymerization (IC50 > 20 μM) nor CDK activity at a single concentration of 10 μM, suggesting alternative targets than tubulin and CDK for the compounds.
View MoreHangzhou JINLAN Pharm-Drugs Technology Co., Ltd
website:http://www.jlpharms.com
Contact:+86-571-86982636
Address:Rm A606, Fuyi Center, jianqiao street, Jianggan Area
Shandong Jiulong Hisince Pharmaceutical Co.,Ltd.
Contact:+86-15853188990
Address:Huadian Pioneer Park, Huadian Township, Qihe County, Dezhou City, Shandong, P.R.China
Contact:+86-21-38122007
Address:2, Lane 1123, Kangqiao Road, Pudong New Area, Shanghai
Shanghai Mokai Pharmaceutical Co.,Ltd
Contact:021-60257269
Address:Rm506,No.915,Zhenbei Road,Shanghai,200333,China
Chongqing KonAo Health Co.,Ltd
Contact:13687578375
Address:wuhan hubei china
Doi:10.1002/chem.201303865
(2014)Doi:10.1134/S1070363212040159
(2012)Doi:10.1039/c2ob25580d
(2012)Doi:10.1016/j.tetlet.2012.04.078
(2012)Doi:10.1039/c2ob25061f
(2012)Doi:10.1248/cpb.39.2219
(1991)