Metallointercalators

Metallointercalators:
Potent in vitro Cytotoxic Agents

• Professor Janice Aldrich-Wright (School of Biomedical & Health Sciences, the Head of the Biologically Active Drugs by Design Group)

PhD Candidates

Masters Candidates

Past Students (PDF, 87kb)

Aldrich-Wright Group;

Keywords: anticancer, metallointercalators, biological activity, NMR, platinum

Collaborators (internal): Prof. W.S. Price (SBHS), A/Prof V. Higgins (SBHS), Dr S. Myers (SBHS), Dr M. Temple(SBH), Prof J. Coorssen (SoM)

Collaborators (external): Dr P. J. Bednarski (Ernst-Moritz-Arndt-Universität, Parmazeutische/Medizinische Chemis, Greifswald,Germany) Dr J. G. Collins (University of New South Wales, ADFA) Dr S. Kelly (Glasgow University)  Dr A. Rodger (University of Warwick, UK) Dr T. Tanase (Nara Women’s University, Japan) Prof. Y. Tor (University of California, San Diego, USA) Dr S. B. Wild (Australian National University) Dr M. J. Tilby (Northern Institute for Cancer Research, University of Newcastle upon Tyne, U.K, Prof A. Bolhuis (University of Bath, for antibacterial testing) Professor B. Chauffert (Burgundy University, Dijon, France) Dr F Bouyer (Burgundy University, Dijon, France) Associate Professor S. Ralph (University of Wollongong) J. J. Beck (University of Wollongong) Viktor Brabec(Institute of Biophysics, Academy of Sciences, Czech Republic) Dr D. Le Pevelenc (Chiralabs Limited Oxford University)

Research: Within our group we have developed new types of metallodrugs, which bind to DNA by various mechanisms such as intercalation, groove binding and coordination. Our range of metallodrugs includes a soluble transplatin analogue with an attached cyclodextrin; groove binding, intercalating and sequence selective compounds, intercalating platinum complexes such as [Pt(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)]Cl2 (56MESS), homonuclear bisintercalating compounds complexes based on (2,2′:6′,2′′-terpyridine)platinum(II) or [(dpq)2Ru(phen-n-SOS-n-phen)Ru(dpq)2]4+ and trinuclear heteronuclear covalent binding metal complexes. From this group, a lead drug has been identified, 56MESS, which has shown activity better than cisplatin in several cell lines. Each compound has been designed to bind to DNA by different mechanisms and we are assessing the effectiveness of these strategies by measuring the effects on cell proliferation and viability.

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Professor Janice Aldrich-Wright - Group Leader

B.App.Sc.(Hons) UTS, PhD. (Macquarie University) MRACI Research; Assoc. Prof. Aldrich-Wright has made significant contributions to the investigation of metal complex-DNA interactions. Her PhD was recognized by the award of the Cornforth Medal by the Royal Australian Chemical Institute in 1994. The medal is awarded annually for the most outstanding PhD thesis submitted in a branch of chemistry, chemical science or chemical technology. The medal is designed to give recognition of outstanding achievement in chemistry and to promote chemical communication. Work initiated in her laboratory at UWS, demonstrated by 1H NMR that ruthenium complexes, delta-[Ru(2,9-Me2phen)2(dpq)]2+ and lamda-[Ru(2,9-Me2phen)2(dpq)]2+ bind to the oligonucleotide d(GTCGAC)2 by intercalation within the minor groove. These were the first octahedral metal complexes reported to exhibit minor-groove intercalation. Research conducted at UWS and in collaboration with Dr R. Fenton (University of Sydney) has resulted in the discovery of a new group of platinum-based compounds. This new group of compounds are water-soluble and in preliminary testing against cancer cells lines show a very high level of activity. As a consequence, these novel compounds are the focus of a Patent. Research based on the synthesis of metallo-polyamides able to target specific base sequences in DNA with high selectivity is the focus of a second International Patent (UWS). In collaboration with A/Prof. S Ralph (UOW), Dr Aldrich-Wright has been investigating the effectiveness of ESI Mass Spectrometry for studying the interactions of metallointercalators with biomolecules. A/Prof. Aldrich-Wright’s has over 70 paper, 2 patents and 5 book chapters with 688 citations to that work. Her 1998 pedagogical paper on DNA-NMR binding (Inorg. Chem., 37 (13), 3133-3141) has been cited more than 167 times in the literature.

J R Aldrich-Wright Publications (PDF, 108kb)
J R Aldrich-Wright Curriculum Vitae (PDF, 117kb)

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Ph D Students

Sharon Kemp  

“Anticancer Dna Intercalators & Their Encapsulation Within Cucurbit[n]Urils”

BSc(Medical Chemistry), BSc (Honours, Class 1), PhD candidate since 2005

Awards:

• Australian postgraduate Award and Top-Up (2006)

S Kemp Publications (PDF, 20kb) 

Maxine Grant
"Cyclodextrins as drug delivery carriers and solubilising anticancer agents."

BSc(Medical Chemistry), BSc (Honours, Class 1), PhD candidate since 2006
On completion of my PhD I would like to get experience as a Post Doc somewhere overseas, then return to the research arena in Australia.
Work Experience;
2006-09 Supervised & demonstrated for Organic Chemistry 2 & 3 practical sessions.
2007-09 Supervised & demonstrated for Chemistry 1 practical sessions.
2007-09 Carried out Tutorials for Chemisty 1 sessions.
Assisted with Siemens Science experiments, running practical sessions for High Schools students and promoting USW
2007-09 Tutorials for NMR Spectroscopy.
2007 Supervised & demonstrated for Pharmalogical Chemistry practical sessions.

Awards:

• UWS postgraduate Award and Top-Up (2006)
• UWS Innovation Conference Best Presentation (2007)

M P Grant Publication (PDF, 10kb)

Nikita Orkey

BSc (Medical Chemistry), BSc (Honours, Class 1), PhD candidate since 2006

N Orkey Publications (PDF, 18kb)

Anwen Krause-Heuer
"Molecular interactions of platinum(II) anticancer agents"

BSc (Advanced Science), BSc (Hons), Class I

Ever since high school I have really enjoyed chemistry, so it was a natural progression for me to complete a chemistry major in my undergraduate degree.  I really enjoyed the work that I completed during my Honours project, I love the challenge of solving some of the puzzles that chemistry can present you with.  This really cemented for me that I would like to continue in research.  I am now completing my PhD with a focus on some of the molecular interactions of platinum intercalating agents.  At the moment I am unsure of where I will be after I finish my PhD, although I would quite like to work in a commercial setting.
I was lucky enough to work over the summer in both 2005/2006 and 2006/2007 at Ceramisphere, located at the Australian Nuclear Science and Technology Organisation (ANSTO).  Here I was working on projects involving the synthesis of silica microparticles, which are tailored for the encapsulation and controlled release of active molecules.
At UWS I participate in undergraduate teaching for a variety of subjects, including: Principles of Chemistry, Introduction to Medicinal Chemistry, Pharmacological Chemistry, Inorganic Chemistry, and Organic Chemistry.
I have also participated in the Siemens Science Experience since 2007, which involves giving high school students a taste of what science is about.  We apply some fundamentals of chemistry to some fun experiments, such as the synthesis of slime, and the chromatography of smarties.

Awards:

• UWS Vice Chancellor Scholarship
• ANSTO Scholarship
• UWS postgraduate Award and Top-Up (2007)
• UWS Innovation Conference Best Poster Presentation (2007)

A M Krause-Heuer Publications (PDF, 45kb)

Benjamin Harper

“The synthesis, characterisation and biological activity of novel platinum(II) intercalators as potential anticancer compounds”

BSc (Medical Chemistry), BSc (Honours, Class 1), PhD candidate since 2009

Awards:

• Confocal Bio-Imaging Facility Honours Awards (2008)
• UWS postgraduate Award and Top-Up (2009)

Benjamin Singh

"Investigation of novel intercalators for use in platinum (II) anticancer complexes."

BSc (Medical Chemistry), BSc (Honours, Class 2.1), PhD candidate since 2009

Awards:

• Confocal Bio-Imaging Facility Honours Awards (2008)
• UWS postgraduate Award and Top-Up (2009)

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Masters Candidates

Madhura Manohar

"Evaluation fo lipids as transport vehicles for platinum (II) complexes."

BSc (Science), BSc (Hons), Class 2.2

On completion of my masters I would like to continue research in the field and eventually obtain a Post Doc position.

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