Cytotoxic 1,4-bis(2-oxo-1-cycloalkylmethylene)benzenes and related compounds

Jonathan R. Dimmock, Amitabh Jha, Praveen Kumar, Gordon A. Zello, J. Wilson Quail, Eliud O. Oloo, Jennifer J. Oucharek, Mohammed K. Pasha, Dallas Seitz, Rajendra K. Sharma, Theresa M. Allen, Cheryl L. Santos, Elias K. Manavathu, Erik De Clercq, Jan Balzarini, James P. Stables

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

A series of 1,4-bis(2-oxo-1-cycloalkylmethylene)benzenes 2a-c and 4 and a related acyclic analogue 6a were synthesised and converted to the corresponding Mannich bases 3a-c, 5 and 6b. Evaluation of these compounds against murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes revealed that the Mannich bases were more cytotoxic than the corresponding unsaturated ketones. 1,4-bis(3-Dimethylaminomethyl-2-oxo-1-cyclohexylmethylene)benzene dihydrochloride (3a) had lower IC50 values than melphalan against the four cell lines and was 15 times more potent than this drug when examined against a panel of human tumours.

Original languageEnglish (US)
Pages (from-to)35-44
Number of pages10
JournalEuropean Journal of Medicinal Chemistry
Volume37
Issue number1
DOIs
StatePublished - Jan 1 2002

Keywords

  • Cytotoxicity
  • Mannich bases
  • N-myristoyltransferase
  • X-ray crystallography
  • α,β-unsaturated ketones

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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    Dimmock, J. R., Jha, A., Kumar, P., Zello, G. A., Quail, J. W., Oloo, E. O., Oucharek, J. J., Pasha, M. K., Seitz, D., Sharma, R. K., Allen, T. M., Santos, C. L., Manavathu, E. K., De Clercq, E., Balzarini, J., & Stables, J. P. (2002). Cytotoxic 1,4-bis(2-oxo-1-cycloalkylmethylene)benzenes and related compounds. European Journal of Medicinal Chemistry, 37(1), 35-44. https://doi.org/10.1016/S0223-5234(01)01294-6