Novel Disulfides with Antitumour Efficacy and Specificity

Rebecca Griffiths; W. Wei-Lynn Wong; Stephen P. Fletcher; Linda Z. Penn; Richard F. Langler

doi:10.1071/CH03105

RESEARCH ARTICLE

Novel Disulfides with Antitumour Efficacy and Specificity

Rebecca Griffiths ^A ^D , W. Wei-Lynn Wong ^A ^B ^D , Stephen P. Fletcher ^C , Linda Z. Penn ^A ^B ^E and Richard F. Langler ^C ^F

+ Author Affiliations

- Author Affiliations

^A Ontario Cancer Institute, University Health Network, 610 University Avenue, Toronto M5G 2M9, Canada.

^B Department of Medical Biophysics, University of Toronto, Toronto M5G 2M9, Canada.

^C Department of Chemistry, Mount Allison University, Sackville, New Brunswick E4L 1G8, Canada.

^D These authors contributed equally to the work.

^E Corresponding author (biological testing). Email: lpenn@oci.utoronto.ca

^F Corresponding author (organic chemistry). Email: rlangler@mta.ca

Australian Journal of Chemistry 58(2) 128-136 https://doi.org/10.1071/CH03105
Submitted: 22 April 2003 Accepted: 16 June 2004 Published: 21 February 2005

Abstract

Some disulfides have previously been shown to possess antifungal and/or antileukaemic activity. Importantly, this cytotoxicity can be selective. We have previously shown that a subset of these compounds does not block the proliferative potential of normal, non-transformed cells. Based on these results and proposed mechanisms of action, a new set of structurally modified organosulfur compounds, including α-substituted disulfides and a thiosulfonate ester, have been prepared and evaluated for their potential as antileukaemic agents. Compounds were screened for antiproliferative activity against a panel of human cells derived from acute lymphocytic and acute myelogenous leukaemia, as well as non-transformed cells. We have identified five new disulfides and a thiosulfonate that can trigger tumour cells to undergo cell death by an apoptotic mechanism in a sensitive and specific manner.

Acknowledgments

This work was supported by MedInnova Partners. The authors acknowledge technical assistance from P. O’Connor. Highfield NMR spectra were obtained by D. Durant. Mass spectra were run by R. Smith. The authors also thank Dr M. D. Minden and Dr M. H. Freedman for providing our AML and ALL cell lines, respectively. W.W.-L.W. is supported by a CIHR Doctoral Award.

References

Novel Disulfides with Antitumour Efficacy and Specificity

Abstract

Acknowledgments

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