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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)325-332
Number of pages8
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume18
Issue number4
DOIs
StatePublished - Aug 1 2003

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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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