Dr Andrea Brancale - PhD
Dr. Brancale’s group main research is focused on the use of computer-aided techniques in the design and discovery of novel anti-viral and anti-cancer compounds. Some representative projects are described below.
Design of novel Hepatitis C Helicase inhibitors.
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
Development of a haptic-driven molecular modeling environment
The development of many modelling software packages is often oriented toward limiting the human intervention, considered to be the bottleneck of the process. The user carries out preparation of the input and analysis of the output, leaving the rest of the discovery process to the computer. Indeed, the use of these methodologies has led to many successes, but it would be fair to ask us if a process that relies mostly on computer pseudo-knowledge whilst, marginalizing researcher knowledge, could be really considered a rational approach.
We are developing a novel immersive molecular modelling simulator where the user uses a haptic device to probe a biological target and its interactions with a potential drug, feeling the forces and molecular interactions on his/her hand while having complete three dimensional visual feedback.
- Computer-aided Drug Design methodologies (De Novo drug design, Virtual screening, homology modelling)
- Organic synthetic chemistry
- Analytical spectroscopy (NMR, mass spectrometry)
Research Funding (current)
- Cancer Research Wales, 2013/16 “Discovery of Bcl-3 inhibitors as potential treatment in metastatic breast cancer”
- EU - FP7-PEOPLE-2010-ITN, 2011/2015, “EUVIRNA- European Training Network on (+)RNA Virus Replication and Antiviral”– www.euvirna.eu
- Biovitas inc. 2010/12, “Computer-aided design of novel HCV helicase inhibitors”.