Dr Fred Widmer

Centre for Infectious Diseases and Microbiology

• Research Interests
• Patents
• Publications
• Contact Details

Dr Fred Widmer is a Senior Research Scientist working in a multi-disciplinary group investigating phospholipase enzymes of pathogenic fungi by molecular biological-, biochemical-, protein chemical-, and medicinal chemistry methods. His specific focus is on the discovery and development as novel antifungal agents of inhibitor(s) against the phospholipase B from Cryptococcus neoformans. This enzyme has been shown by the group to be a virulence factor and, as such, provides a novel antifungal drug target.

He is also developing a new class of enzyme substrates for in-vitro and in-vivo diagnostic applications.

The work on the phospholipase inhibitors has resulted in two patent filings (on novel bis-cationic compound classes), and the discovery that Miltefosine, a drug licensed to treat leishmaniasis, is strongly and broadly antifungal. This discovery resulted in a collaboration with the pharmaceutical company Zentaris GmbH, Frankfurt , Germany , and earned him a Science Alumni of Honour Award from the University of Waterloo, Ontario, Canada in 2007 (www.science.uwaterloo.ca/alumni/awards/50.html)

Dr Widmer is a member of the Swiss Chemical Society and the Australian Society for Biochemistry & Molecular Biology.

Research Interests

Earlier in his career Dr Widmer’s interests were limited to synthetic methodology in peptide chemistry but over time he became more and more involved in drug discovery and development. Initially, his focus was on methodology and technology. Now it is on pharmaceutical and diagnostic products, as well as on tools for research.

His main interests now are:

• Novel amino-carbonyl compounds and their assembly into pharmacologically active structural configurations. The assembly is either single compound or in libraries of appropriate complexity. The structural concept relies heavily on earlier work on peptide-related compounds, and, from the outset, considers essential aspects of bioavailability and chemical-, physical-, metabolic- and microbial stability.
• All aspects of drugs, i.e. medicinal-, pharmaceutical-, pharmacological-, as well as formulation- and delivery aspects.
• Discovery and development of novel antifungal chemical entities on the basis of the working hypothesis that phospholipase(s) from pathogenic fungi are antifungal drug target(s).
• Novel class of enzyme substrates for diagnostic and sensor industry.

In addition to the hands-on experience during his work at the Weizmann Institute, the NIH, at Carlsberg Biotechnology Ltd and Peptide Technology Ltd., the CSIRO and in his current position, Dr Widmer has acquired a substantial knowledge and understanding of the approaches, processes and nuances of drug discovery, design and development by attending numerous conferences, symposia and workshops on medicinal- and pharmaceutical chemistry, drug delivery, formulation and ADME work. He has established an extensive international network on all aspects of drug discovery and development.

Patents

• Bis-cationic Compounds and Use Thereof.
  Inventors: Widmer Alfred (Fred) Werner, Jolliffe Katrina Anne, Wright Lesley Catherine and Sorrell Tania Christine. Australian Provisional Patent Application (Application Number AU2003906261).
  Filed: November 13, 2003. Entered PCT phase on November 13, 2004.
  International Publication Date: 26 May 2005.
  International Publication Number: WO 2005/047230.
• Bis-pyridinium compounds.
  Inventors: Jolliffe Katrina Anne and Widmer Alfred (Fred) Werner. Australian Provisional Patent Application (Application Number: AU2006902367). Filed: May 5, 2006. Entered PCT phase on May 4, 2007.
  International Application Number: PCT/AU2007/000594.
  International Publication Date: November 15, 2007.
  International Publication Number: WO 2007/128059.

Publications

- 2008 - 2007 - 2006 - 2004 - 2002 - 2001 - 2000 -

2008

• Chen SC., Tong ZS., Lee OC., Halliday C., Playford EG., Widmer F., Kong FR., Wu C. and Sorrell TC. Clinician response to Candida organisms in the urine of patients attending hospital. Eur J Clin Microbiol Infect Dis. 27, 201-208, 2008. [Abstract]
• Treerat P., Widmer F., Middleton P., Iredall J. and George A. In vitro interactions of tobramycin with various nonantibiotics against Pseudomonas aeruginosa and Burkholderia cenocepacia. FEMS Microbiol. Lett., 285, 40-50, 2008. [Abstract]

2007

• C. K. L. Ng, V. Singhal, F. Widmer, L. C. Wright, T. C. Sorrell and K. A. Jolliffe, Synthesis, Antifungal and Hemolytic Activity of a Series of Bis(pyridinium)alkanes. Bioorg. Med. Chem. 15, 3422-3429, 2007. [Abstract]
• Z. Tong, F. Widmer, T. C. Sorrell, Z. Guse, K. A. Jolliffe, C. Halliday, O. C. Lee, F. Kong, L. C. Wright and S. C. A. Chen, In-vitro activity of miltefosine and two novel antifungal bis-cationic salts against a panel of 77 dermatophytes. Antimicrob. Agents Chemother. 51(6), 2219-2222, 2007. [Abstract]
• D. Obando, F. Widmer, L. C. Wright, T. C. Sorrell and K. A. Jolliffe, Synthesis, Antifungal and Antimicrobial Activity of Alkylphospholipids. Bioorg. Med. Chem. 15, 5158-5165, 2007. [Abstract]

2006

• Ng CK, Obando D, Widmer F, Wright LC, Sorrell TC and Jolliffe KA, Correlation of antifungal activity with fungal phospholipase inhibition using a series of bisquaternary salts. J. Med. Chem., 49(2), 811-816, 2006. [Abstract]
• Widmer F , Wright LC, Obando D, Hanke R. Ganendren R, Ellis DH and Sorrell TC, Hexadecylphosphocholine (miltefosine) has broad-spectrum fungicidal activity and is efficacious in a mouse model of cryptococcosis. Antimicrob. Agents Chemother. 50(2), 414-421, 2006. [Abstract]
• Ganendren R, Carter E, Sorrell T, Widmer F and Wright L, Phospholipase B activity enhances adhesion of Cryptococcus neoformans to a human lung epithelial cell line. Microbes Infect. 8(4), 1006-1015, 2006. [Abstract]

2004

• R. Ganendren, F. Widmer, V. Singhal, C. Wilson, T. Sorrell and L.Wright: In-vitro antifungal activity of inhibitors of secretory, and newly characterised cell-associated phospholipases from the fungal pathogen, Cryptococcus neoformans. Antimicrobial Agents and Chemotherapy, 48(5), 1561-1569, 2004 [Abstract]
• Wright LC, Payne J, Santangelo RT, Simpanya MF, Chen SC , Widmer F, Sorrell TC: Cryptococcal phospholipases: a novel lysophospholipase discovered in the pathogenic fungus Cryptococcus gattii. Biochem J. 2004 Dec 1;384(Pt 2):377-84. [Abstract]

2002

• Craig L. Francis, Qi Yang, Noel K. Hart, Fred Widmer, Michael K. Manthey, and H. Ming He-Williams: Total Synthesis of Methotrexate-TRIS –Fatty Acid Conjugates. Aust. J. Chem. 55, 635-645, 2002
• R.A Davey, M.W. Davey, K.V. Cullen, X.E. Wells, C.L. Francis, H-M. Williams, Q. Yang, M.J. Moghaddam, F. Widmer, and R.G. Whittaker: The Use of Tris-Lipidation to modify drug interactions with P-glycoprotein and MRP1. Br. J. Pharmacol. 137, 1280-1286, 2002. [Abstract]
• C. Walker, J.M. Fraser, C.E. Walton, F. Widmer, C.L. Francis, Q. Yang, M. O’Sullivan, R.G. Whittaker and X.E. Wells: Tris-Lipidatin – A novel drug delivery system that alters biodistribution. Journal of Drug Targeting, 10(6), 479-487, 2002 [Abstract]

2001

• Cathrine Walker, Clayton Walton, Julie Petkovich, Xanthe Wells, Fred Widmer, and Robert Whittaker: A simple and rapid semi-quantitative screening technique for storage-phosphor whole body autoradiography. J. Pharmac. Toxicol. Methods 45, 241-246, 2001.

2000

• Fred Widmer , Patricia J. Hayes, Robert G. Whittaker and Rakesh K. Kumar: Substrate preference profiles of protease activities released by allergenic pollens. Clin. Exp. Allergy 30, 571-576, 2000. [Abstract]

Contact Details

T +61 2 9845 7863

F +61 2 9856 8016

E fredw@icpmr.wsahs.nsw.gov.au