1196448-95-9Relevant academic research and scientific papers
Synthesis and pharmacological exploitation of clioquinol-derived copper-binding apoptosis inducers triggering reactive oxygen species generation and MAPK pathway activation
Chen, Hui-Ling,Chang, Chun-Yi,Lee, Hsun-Tzu,Lin, Hua-Hsuan,Lu, Pei-Jung,Yang, Chia-Ning,Shiau, Chung-Wai,Shaw, Arthur Y.
, p. 7239 - 7247 (2009)
In the present study, we carried out Mannich-type reaction to synthesize clioquinol-derived 7-methyl-arylsulfonylpiperazine analogs with improved growth-inhibitory effects. 11 bearing 5-nitro group on the quinoline ring exhibited 26-fold more potent than that of clioquinol against HeLa cells with a GI50 value of 0.71 μM. In addition, 11 revealed synergistic effects on the growth inhibition of HeLa cells with GI50 values of 0.65, 0.25, and 0.06 μM in the presence of 1, 10, and 50 μM copper, respectively. Consistent to the clioquinol-mediated apoptosis, mechanistic study indicates that 9- and 11-induced growth inhibition is attributed to caspase-dependent pathway. Detection of reactive oxygen species in response to clioquinol, 9 and 11 confirmed that ROS was dramatically stimulated in the presence of copper and partially abolished upon treatment of 1 mM tempol. Further study indicated that 9- and 11-mediated induction of oxidative stress by ROS generation resulted in the activation MAPK pathway.
Synthesis and structure-activity relationship study of 8-hydroxyquinoline- derived Mannich bases as anticancer agents
Shaw, Arthur Y.,Chang, Chun-Yi,Hsu, Mei-Yuan,Lu, Pei-Jung,Yang, Chia-Ning,Chen, Hui-Ling,Lo, Cheng-Wei,Shiau, Chung-Wai,Chern, Ming-Kai
experimental part, p. 2860 - 2867 (2010/08/20)
To continue our early study on the structural modifications of clioquinol, more 8-hydroxyquinoline-derived Mannich bases were synthesized and examined for growth-inhibitory effect. Taken Mannich base 1 as our lead compound, upon replacement of either sulfonyl group with methylene group or piperazine ring with ethylenediamine group resulted in an appreciable increase in potency. On the other hand, as 8-hydroxyquinoline was replaced with phenol, 3-hydroxypyridine and 1-naphthol, a dramatic decrease in activity was observed, indicating that 8-hydroxyquinoline is a crucial scaffold for activity. Further 3D-QSAR analysis on HeLa cells revealed that both steric and electronic effects contributed equally to growth inhibition. Taken together, the structure-activity relationships obtained from both in vitro data and CoMFA model warrant a valuable reference for further study.
