Synthesis and structure-activity relationship study of 8-hydroxyquinoline-derived Mannich bases as anticancer agents.
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.
Shaw
Arthur Y
AY
Department of Chemistry, Tamkang University, Danshui 251, Taiwan. shaw.299@gmail.com
Chang
Chun-Yi
CY
Hsu
Mei-Yuan
MY
Lu
Pei-Jung
PJ
Yang
Chia-Ning
CN
Chen
Hui-Ling
HL
Lo
Cheng-Wei
CW
Shiau
Chung-Wai
CW
Chern
Ming-Kai
MK
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008352:Mannich Bases / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D015125:Oxyquinoline / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship
D000970:Antineoplastic Agents; D008352:Mannich Bases; D015125:Oxyquinoline