Synthesis and structure-activity relationship study of 8-hydroxyquinoline- derived Mannich bases as anticancer agents

Arthur Y. Shaw; Chun Yi Chang; Mei Yuan Hsu; Pei Jung Lu; Chia Ning Yang; Hui Ling Chen; Cheng Wei Lo; Chung Wai Shiau; Ming Kai Chern

doi:10.1016/j.ejmech.2010.03.008

Synthesis and structure-activity relationship study of 8-hydroxyquinoline- derived Mannich bases as anticancer agents

Arthur Y. Shaw, Chun Yi Chang, Mei Yuan Hsu, Pei Jung Lu, Chia Ning Yang, Hui Ling Chen, Cheng Wei Lo, Chung Wai Shiau, Ming Kai Chern

Institute of Clinical Medicine

Research output: Contribution to journal › Article › peer-review

63 Citations (Scopus)

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.

Original language	English
Pages (from-to)	2860-2867
Number of pages	8
Journal	European Journal of Medicinal Chemistry
Volume	45
Issue number	7
DOIs	https://doi.org/10.1016/j.ejmech.2010.03.008
Publication status	Published - 2010 Jul

All Science Journal Classification (ASJC) codes

Pharmacology
Drug Discovery
Organic Chemistry

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10.1016/j.ejmech.2010.03.008

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@article{082c96664d4b4160a8c3d9e5a31b9a02,

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.",

author = "Shaw, {Arthur Y.} and Chang, {Chun Yi} and Hsu, {Mei Yuan} and Lu, {Pei Jung} and Yang, {Chia Ning} and Chen, {Hui Ling} and Lo, {Cheng Wei} and Shiau, {Chung Wai} and Chern, {Ming Kai}",

note = "Funding Information: Financial support from the National Science Council of the Republic of China and Tamkang University to A. Y. Shaw is gratefully acknowledged. Copyright: Copyright 2010 Elsevier B.V., All rights reserved.",

year = "2010",

month = jul,

doi = "10.1016/j.ejmech.2010.03.008",

language = "English",

volume = "45",

pages = "2860--2867",

journal = "European Journal of Medicinal Chemistry",

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T1 - Synthesis and structure-activity relationship study of 8-hydroxyquinoline- derived Mannich bases as anticancer agents

AU - Shaw, Arthur Y.

AU - Chang, Chun Yi

AU - Hsu, Mei Yuan

AU - Lu, Pei Jung

AU - Yang, Chia Ning

AU - Chen, Hui Ling

AU - Lo, Cheng Wei

AU - Shiau, Chung Wai

AU - Chern, Ming Kai

N1 - Funding Information: Financial support from the National Science Council of the Republic of China and Tamkang University to A. Y. Shaw is gratefully acknowledged. Copyright: Copyright 2010 Elsevier B.V., All rights reserved.

PY - 2010/7

Y1 - 2010/7

N2 - 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.

AB - 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.

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JO - European Journal of Medicinal Chemistry

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IS - 7

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Synthesis and structure-activity relationship study of 8-hydroxyquinoline- derived Mannich bases as anticancer agents

Abstract

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