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 Kurian Manavathu, Erik De Clercq, Jan Balzarini, James P. Stables

Research output: Contribution to journalArticle

31 Citations (Scopus)

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

Fingerprint

Tetralones
Toxicity
Cells
Melphalan
T-cells
Biosynthesis
Tumor Cell Line
Antineoplastic Agents
Colonic Neoplasms
Nucleic Acids
Oxidation-Reduction
Tumors
T-Lymphocytes
Molecules
Proteins

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Dimmock, J. R., Padmanilyam, M. P., Zello, G. A., Wilson Quail, J., Oloo, E. O., Prisciak, J. S., ... 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

Cytotoxic 1,3-diarylidene-2-tetralones and related compounds. / Dimmock, Jonathan R.; Padmanilyam, Maniyan P.; Zello, Gordon A.; Wilson Quail, J.; Oloo, Eliud O.; Prisciak, Jared S.; Kraatz, Heinz Bernhard; Cherkasov, Arten; Lee, Jeremy S.; Allen, Theresa M.; Santos, Cheryl L.; Manavathu, Elias Kurian; De Clercq, Erik; Balzarini, Jan; Stables, James P.

In: European Journal of Medicinal Chemistry, Vol. 37, No. 10, 01.10.2002, p. 813-824.

Research output: Contribution to journalArticle

Dimmock, JR, Padmanilyam, MP, Zello, GA, Wilson Quail, J, Oloo, EO, Prisciak, JS, Kraatz, HB, Cherkasov, A, Lee, JS, Allen, TM, Santos, CL, Manavathu, EK, De Clercq, E, Balzarini, J & Stables, JP 2002, 'Cytotoxic 1,3-diarylidene-2-tetralones and related compounds', European Journal of Medicinal Chemistry, vol. 37, no. 10, pp. 813-824. https://doi.org/10.1016/S0223-5234(02)01402-2
Dimmock JR, Padmanilyam MP, Zello GA, Wilson Quail J, Oloo EO, Prisciak JS et al. Cytotoxic 1,3-diarylidene-2-tetralones and related compounds. European Journal of Medicinal Chemistry. 2002 Oct 1;37(10):813-824. https://doi.org/10.1016/S0223-5234(02)01402-2
Dimmock, Jonathan R. ; Padmanilyam, Maniyan P. ; Zello, Gordon A. ; Wilson Quail, J. ; Oloo, Eliud O. ; Prisciak, Jared S. ; Kraatz, Heinz Bernhard ; Cherkasov, Arten ; Lee, Jeremy S. ; Allen, Theresa M. ; Santos, Cheryl L. ; Manavathu, Elias Kurian ; De Clercq, Erik ; Balzarini, Jan ; Stables, James P. / Cytotoxic 1,3-diarylidene-2-tetralones and related compounds. In: European Journal of Medicinal Chemistry. 2002 ; Vol. 37, No. 10. pp. 813-824.
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