Faculty of Science School of Chemistry

David McFadyen

Associate Professor

CONTACT DETAILS:

Address: School of Chemistry, University of Melbourne, Parkville, VIC 3010 Australia

Room: 183

Email: wdmf@unimelb.edu.au

 

Field of expertise

Metal-based Drugs

Our research activities are centred around the rational design, synthesis, physical study and biological evaluation of small molecules which interact with DNA, with particular reference to their potential use as antitumour agents. Two broad categories of compound are of current interest: platinum(II) amine complexes and photo-activated prodrugs.
  • Platinum complexes
    We are extensively investigating diamine Pt complexes tethered to DNA intercalating chromophores (eg. structure 1). These complexes are designed to target platinum to DNA. Chromophores used to date have included acridines,[4] phenazine [2] and phenanthridine. Targeting to DNA represents one strategy which may circumvent problems of drug resistance. We are also exploring ways of directing platination away from the normal coordination sites in the DNA major groove to nucleophilic base sites in the minor groove.
  • Photo-activated prodrugs
    This aspect of the program is concerned with the development of photoactivated prodrug systems consisting of a light absorber / donor unit (D) which is electronically excited upon photoirradiation. Photo-induced electron transfer may occur via a linker framework to a M(III)/(II) electron acceptor unit (A), which, when reduced, causes the release of a coordinated ligand. This ligand could be a drug molecule such as a cytotoxic DNA alkylating agent.

    We are presently exploring this concept using systems in which anthracene donors are linked to metal macrocycles. An example of such a molecule is provided by structure 2 where M = Co(III) and L is an axial ligand.

 

Selected Publications:
  1. Temple, M.; McFadyen, W. D.; Holmes R. J.; Denny, W. A.; Murray, V., Biochemistry 2000: 39, 5593-5599.
  2. Holmes, R. J.; Mc Keage, M. J.; Murray, V.; Denny, W. A.; McFadyen, W. D., J. Inorg. Biochem. 2001: 85, 209-217.
  3. Funston, A. M.; McFadyen, W. D.; Tregloan, P. A.; J. Chem. Soc., Dalton Trans., 2002: 8, 2053-2060.
  4. Funston, A. M.; Ghiggino, K. P.; Grannas, M. J.; McFadyen, W. D.; Tregloan, P. A., Dalton Trans. 2003: 19, 3704-3712.
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