Cytotoxic analogues of 2,6-bis(arylidene)cyclohexanones

Jonathan R. Dimmock, Maniyan P. Padmanilayam, Gordon A. Zello, Kurt H. Nienaber, Theresa M. Allen, Cheryl L. Santos, Erik De Clercq, Jan Balzarini, Elias Kurian Manavathu, James P. Stables

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

A series of 2,6-bis(arylidene)cycloalkanones (1) and related compounds containing one or two substituents at the four position of the cyclohexyl ring were prepared and shown to display cytotoxic activity towards murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In some of the series of compounds, positive correlations were noted between the potencies of the enones and the magnitude of the Hammett σ values of the aryl substituents. Four representative compounds were cytotoxic to a number of human tumours in vitro, particularly towards colon cancer and leukemic cells. A noteworthy feature of the compounds prepared in this study is that, in general, they were well tolerated when administered to rodents. A number of lead molecules emerged from this investigation as well as guidelines for future expansion of these series of compounds.

Original languageEnglish (US)
Pages (from-to)169-177
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Volume38
Issue number2
DOIs
StatePublished - Feb 1 2003

Fingerprint

Cyclohexanones
T-cells
Tumors
Molecules
Colonic Neoplasms
Rodentia
Guidelines
T-Lymphocytes
Neoplasms
Lead

Keywords

  • Bioscreens
  • Cytotoxicity
  • Structure-activity relationships
  • α,β-Unsaturated ketones

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Dimmock, J. R., Padmanilayam, M. P., Zello, G. A., Nienaber, K. H., Allen, T. M., Santos, C. L., ... Stables, J. P. (2003). Cytotoxic analogues of 2,6-bis(arylidene)cyclohexanones. European Journal of Medicinal Chemistry, 38(2), 169-177. https://doi.org/10.1016/S0223-5234(02)01444-7

Cytotoxic analogues of 2,6-bis(arylidene)cyclohexanones. / Dimmock, Jonathan R.; Padmanilayam, Maniyan P.; Zello, Gordon A.; Nienaber, Kurt H.; Allen, Theresa M.; Santos, Cheryl L.; De Clercq, Erik; Balzarini, Jan; Manavathu, Elias Kurian; Stables, James P.

In: European Journal of Medicinal Chemistry, Vol. 38, No. 2, 01.02.2003, p. 169-177.

Research output: Contribution to journalArticle

Dimmock, JR, Padmanilayam, MP, Zello, GA, Nienaber, KH, Allen, TM, Santos, CL, De Clercq, E, Balzarini, J, Manavathu, EK & Stables, JP 2003, 'Cytotoxic analogues of 2,6-bis(arylidene)cyclohexanones', European Journal of Medicinal Chemistry, vol. 38, no. 2, pp. 169-177. https://doi.org/10.1016/S0223-5234(02)01444-7
Dimmock JR, Padmanilayam MP, Zello GA, Nienaber KH, Allen TM, Santos CL et al. Cytotoxic analogues of 2,6-bis(arylidene)cyclohexanones. European Journal of Medicinal Chemistry. 2003 Feb 1;38(2):169-177. https://doi.org/10.1016/S0223-5234(02)01444-7
Dimmock, Jonathan R. ; Padmanilayam, Maniyan P. ; Zello, Gordon A. ; Nienaber, Kurt H. ; Allen, Theresa M. ; Santos, Cheryl L. ; De Clercq, Erik ; Balzarini, Jan ; Manavathu, Elias Kurian ; Stables, James P. / Cytotoxic analogues of 2,6-bis(arylidene)cyclohexanones. In: European Journal of Medicinal Chemistry. 2003 ; Vol. 38, No. 2. pp. 169-177.
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