3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones: A novel group of cytotoxic agents

J. R. Dimmock; A. Jha; G. A. Zello; R. K. Sharma; A. Shrivastav; P. Selvakumar; T. M. Allen; C. L. Santos; J. Balzarini; E. De Clercq; Elias Kurian Manavathu; J. P. Stables

doi:10.1080/1475636031000121938

3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones: A novel group of cytotoxic agents

J. R. Dimmock, A. Jha, G. A. Zello, R. K. Sharma, A. Shrivastav, P. Selvakumar, T. M. Allen, C. L. Santos, J. Balzarini, E. De Clercq, Elias Kurian Manavathu, J. P. Stables

Infectious Disease

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

30 Scopus citations

Abstract

A series of novel 3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones 3 have been synthesized which displayed potent cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. In contrast, the related N-arylmaleamic acids 4 possessed little or no cytotoxicity in these four screens. Molecular modeling revealed certain interplanar and bond angles and interatomic distances which were perceived to contribute to the observed bioactivity as well as providing suggestions for future structural modifications of the piperidones 3. Evaluation of representative compounds in series 3 and 4 on the activity of human N-myristoyltransferase revealed that, at the maximum concentration utilized, namely 250 μM, only weak inhibiting properties were displayed by some of the compounds in series 4. Various members of series 3 and 4 were well tolerated in mice.

Original language	English (US)
Pages (from-to)	325-332
Number of pages	8
Journal	Journal of Enzyme Inhibition and Medicinal Chemistry
Volume	18
Issue number	4
DOIs	https://doi.org/10.1080/1475636031000121938
State	Published - Aug 2003

Keywords

4-piperidones
Cytotoxicity
Human N-myristoyltransferase
Maleamic acids
Molecular modeling

ASJC Scopus subject areas

Pharmacology
Drug Discovery

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10.1080/1475636031000121938

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Dimmock, J. R., Jha, A., Zello, G. A., Sharma, R. K., Shrivastav, A., Selvakumar, P., Allen, T. M., Santos, C. L., Balzarini, J., De Clercq, E., Manavathu, E. K., & Stables, J. P. (2003). 3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones: A novel group of cytotoxic agents. Journal of Enzyme Inhibition and Medicinal Chemistry, 18(4), 325-332. https://doi.org/10.1080/1475636031000121938

Dimmock, JR, Jha, A, Zello, GA, Sharma, RK, Shrivastav, A, Selvakumar, P, Allen, TM, Santos, CL, Balzarini, J, De Clercq, E, Manavathu, EK & Stables, JP 2003, '3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones: A novel group of cytotoxic agents', Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 18, no. 4, pp. 325-332. https://doi.org/10.1080/1475636031000121938

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abstract = "A series of novel 3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones 3 have been synthesized which displayed potent cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. In contrast, the related N-arylmaleamic acids 4 possessed little or no cytotoxicity in these four screens. Molecular modeling revealed certain interplanar and bond angles and interatomic distances which were perceived to contribute to the observed bioactivity as well as providing suggestions for future structural modifications of the piperidones 3. Evaluation of representative compounds in series 3 and 4 on the activity of human N-myristoyltransferase revealed that, at the maximum concentration utilized, namely 250 μM, only weak inhibiting properties were displayed by some of the compounds in series 4. Various members of series 3 and 4 were well tolerated in mice.",

keywords = "4-piperidones, Cytotoxicity, Human N-myristoyltransferase, Maleamic acids, Molecular modeling",

author = "Dimmock, {J. R.} and A. Jha and Zello, {G. A.} and Sharma, {R. K.} and A. Shrivastav and P. Selvakumar and Allen, {T. M.} and Santos, {C. L.} and J. Balzarini and {De Clercq}, E. and Manavathu, {Elias Kurian} and Stables, {J. P.}",

note = "Funding Information: The following sources of financial support for this study (recipient in parentheses) are gratefully acknowledged, namely Purdue Neuroscience Company, USA (J. R. Dimmock), Canadian Institutes of Health Research (R. K. Sharma), National Cancer Institute of Canada (T. M. Allen), Belgian Fonds voor Geneeskundig Wetenschappely¨k Onderzoek (J. Balzarini, E. De Clercq) and the U. S. National Institute of Neurological Disorders and Stroke (J. P. Stables). The secretarial assistance of Ms. B. McCullough is noted with appreciation.",

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doi = "10.1080/1475636031000121938",

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AU - Jha, A.

AU - Zello, G. A.

AU - Sharma, R. K.

AU - Shrivastav, A.

AU - Selvakumar, P.

AU - Allen, T. M.

AU - Santos, C. L.

AU - Balzarini, J.

AU - De Clercq, E.

AU - Manavathu, Elias Kurian

AU - Stables, J. P.

N1 - Funding Information: The following sources of financial support for this study (recipient in parentheses) are gratefully acknowledged, namely Purdue Neuroscience Company, USA (J. R. Dimmock), Canadian Institutes of Health Research (R. K. Sharma), National Cancer Institute of Canada (T. M. Allen), Belgian Fonds voor Geneeskundig Wetenschappely¨k Onderzoek (J. Balzarini, E. De Clercq) and the U. S. National Institute of Neurological Disorders and Stroke (J. P. Stables). The secretarial assistance of Ms. B. McCullough is noted with appreciation.

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N2 - A series of novel 3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones 3 have been synthesized which displayed potent cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. In contrast, the related N-arylmaleamic acids 4 possessed little or no cytotoxicity in these four screens. Molecular modeling revealed certain interplanar and bond angles and interatomic distances which were perceived to contribute to the observed bioactivity as well as providing suggestions for future structural modifications of the piperidones 3. Evaluation of representative compounds in series 3 and 4 on the activity of human N-myristoyltransferase revealed that, at the maximum concentration utilized, namely 250 μM, only weak inhibiting properties were displayed by some of the compounds in series 4. Various members of series 3 and 4 were well tolerated in mice.

AB - A series of novel 3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones 3 have been synthesized which displayed potent cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine P388 and L1210 leukemic cells. In contrast, the related N-arylmaleamic acids 4 possessed little or no cytotoxicity in these four screens. Molecular modeling revealed certain interplanar and bond angles and interatomic distances which were perceived to contribute to the observed bioactivity as well as providing suggestions for future structural modifications of the piperidones 3. Evaluation of representative compounds in series 3 and 4 on the activity of human N-myristoyltransferase revealed that, at the maximum concentration utilized, namely 250 μM, only weak inhibiting properties were displayed by some of the compounds in series 4. Various members of series 3 and 4 were well tolerated in mice.

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3,5-bis(phenylmethylene)-1-(N-arylmaleamoyl)-4-piperidones: A novel group of cytotoxic agents

Abstract

Keywords

ASJC Scopus subject areas

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