Cytotoxic 1,3-diarylidene-2-tetralones and related compounds

Jonathan R. Dimmock, Maniyan P. Padmanilyam, Gordon A. Zello, J. Wilson Quail, Eliud O. Oloo, Jared S. Prisciak, Heinz Bernhard Kraatz, Arten Cherkasov, Jeremy S. Lee, Theresa M. Allen, Cheryl L. Santos, Elias K. Manavathu, Erik De Clercq, Jan Balzarini, James P. Stables

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

A number of 1,3-arylidene-2-tetralones 1, 2 and 4 were synthesised and demonstrated cytotoxic activity towards murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In general, the related 1-arylidene-2-tetralones 3 possessed lower potencies in these screens than the compounds in series 1 and 4. Approximately, half of the compounds were evaluated against a panel of human tumour cell lines. In this screen, most of the enones were more cytotoxic than the established anticancer agent melphalan and some demonstrated selective toxicity towards leukemic and colon cancer cells. The modes of action of representative compounds include interfering with the biosyntheses of nucleic acids and proteins as well as altering redox potentials. The compounds were well tolerated when administered intraperiteonally to mice. Thus these novel enones are promising prototypic molecules due to their potent cytotoxic properties and lack of significant murine toxicity.

Original languageEnglish (US)
Pages (from-to)813-824
Number of pages12
JournalEuropean Journal of Medicinal Chemistry
Volume37
Issue number10
DOIs
StatePublished - Oct 1 2002

Keywords

  • 2-Tetralones
  • Cytotoxicity
  • Murine toxicity
  • Redox potentials

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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    Dimmock, J. R., Padmanilyam, M. P., Zello, G. A., Wilson Quail, J., Oloo, E. O., Prisciak, J. S., Kraatz, H. B., Cherkasov, A., Lee, J. S., Allen, T. M., Santos, C. L., Manavathu, E. K., De Clercq, E., Balzarini, J., & Stables, J. P. (2002). Cytotoxic 1,3-diarylidene-2-tetralones and related compounds. European Journal of Medicinal Chemistry, 37(10), 813-824. https://doi.org/10.1016/S0223-5234(02)01402-2