Welsh School of Pharmacy

A member of the School's    Medicinal Chemistry Research Discipline 

Hepatitis C is a liver infection caused by a flavivirus (HCV) that affects over 170 million people. In most cases the infection becomes chronic and 20% of the carrier develops cirrhosis. Currently the infection is treated with interferon, but this therapy does not completely eliminate the virus and more efficacious treatments are needed. Our interest has been focused on the viral helicase, a fundamental enzyme in the viral replication process. From the observation of the crystal structure of the enzyme, we have identified a possible binding site for a putative inhibitor and, using computer-aided de novo drug design methods, we intend to identify a series of molecules, which could act as inhibitors of the enzyme.

Design and optimisation of novel anti-tubulin agents.

Microtubules are involved in a wide number of cellular functions, such as motility, division, shape maintenance, and intracellular transport. The major protein component found in microtubules is tubulin. Inhibition of microtubule function using tubulin-targeting agents is a validated approach to anti-cancer therapy. We have recently reported the discovery of a novel series of arylthioindoles as potent inhibitors of tubulin polymerisation, which also shown a comparable inhibition of MCF-7 human breast carcinoma cells growth with colchicine and combretastatine. The aim of this project is to optimise the structure and improve the activity of this novel class of compounds with the aid of computer based techniques

Collaborators

• Prof. Johan Netys; Rega Institute, Leuven, Belgium

• Prof. Romano Silvestri; Universituy of Rome “La Sapienza”, Italy

• Prof John Drach; University of Michigan, USA

• Dr. Romeo Romagnoli; University of Ferrara, Italy

• Prof. Mario Sechi; University of Sassari, Italy

• Dr. Dimitrios Vlachakis, National Centre for Scientific Research Demokritos, Greece

• Prof Rudolf Allemann; Cardiff University, UK

• Dr. Jamie Platts; Cardiff University, UK

• Dr. Dafydd Jones; Cardiff University, UK

• Dr. Colin Berry; Cardiff University, UK

Key Expertise

• Computer-aided Drug Design methodologies (De Novo drug design, Virtual screening, homology modelling)

• Organic synthetic chemistry

• Analytical spectroscopy (NMR, mass spectrometry)

Research Funding   (current)

• PhD studentship - Funded by The Embassy of the Arab Republic of Egypt (45,000£); three years (2005/2008).