title: Synthesis and structure-activity relationship study of 8-hydroxyquinoline-derived Mannich bases as anticancer agents.
abstract: 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.
authors.affiliation: Department of Chemistry, Tamkang University, Danshui 251, Taiwan. shaw.299@gmail.com
authors.forename: Arthur Y
authors.initials: AY
authors.lastname: Shaw
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Chang
authors.forename: Mei-Yuan
authors.initials: MY
authors.lastname: Hsu
authors.forename: Pei-Jung
authors.initials: PJ
authors.lastname: Lu
authors.forename: Chia-Ning
authors.initials: CN
authors.lastname: Yang
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Chen
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: Lo
authors.forename: Chung-Wai
authors.initials: CW
authors.lastname: Shiau
authors.forename: Ming-Kai
authors.initials: MK
authors.lastname: Chern
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D008352:Mannich Bases; D015125:Oxyquinoline