Health, Food and Drug Chemistry

Pioneering multidisciplinary development of new technologies and therapeutics

Group Overview

The development of novel potential drugs, drug formulations and delivery systems is a very important research focus for the Chemistry Department. The combined research expertise of the Chemistry staff involved in this research area covers and explores different major areas of drug discovery and health research, from in silico drug design to the evaluation of novel medical solutions in pre-clinical models.

Starting from the study of disease targets and pathways, our mission is to translate novel ideas into new drugs and drug systems.

Our main areas of expertise are:

Computer-Aiderd Drug Design (CADD)
SAR by NMR
Synthesis of new chemical agents and analogue libraries
Multi-action therapeutics
In vitro assays and target validation
Drug Delivery Systems
Chemical communication in agriculture

Affiliated Staff

Current Research Projects

Development of novel antiviral agents for viral diseases caused by infection with flaviviruses, arboviruses, arenaviruses and coronaviruses

OVERVIEW: Computer-aided drug design techniques are applied to study both viral targets and host factors involved in a range of viral diseases. Using computational methods, novel small molecules able to interfere with these targets are designed, then synthesised and evaluated in different enzymatic and cell-based assays, with the aim to develop novel, safe, and selective treatment strategies for a range of important human pathogens.

PROJECT OUTCOMES: Novel small-molecule scaffolds are identified as promising hit and lead molecules for further development into new antiviral therapies.

AFFILIATED STAFF: Dr Marcella Bassetto

RESEARCH CENTRES/GROUPS: Rega Institute for Medical Research, Leuven Belgium, Institut für Mikrobiologie der Bundeswehr, Munich, Germany, Utah State University, USA

COLLABORATIVE/ENGAGEMENT OPPORTUNITIES: We are always open to establish new collaborations with biologists, virologists and fellow medicinal chemists to explore new targets and strategies to identify novel antiviral agents.

PUBLICATIONS:

Ferla, S., Manganaro, R., Benato, S., Paulissen, J., Neyts, J., Jochmans, D., Brancale, A., Bassetto, M. 2020 Rational modifications, synthesis and biological evaluation of new potential antivirals for RSV designed to target the M2-1 protein. Bioorganic & Medicinal Chemistry 28, 8, 115401; doi: 10.1016/j.bmc.2020.115401.

Giancotti, G., Rigo, I., Pasqualetto, G., Young, M., Neyts, J., Rocha-Pereira, J., Brancale, A., Ferla, S., Bassetto, M. 2019 A new antiviral scaffold for human norovirus identified with computer-aided approaches on the viral polymerase. Scientific Reports, 9, 1; doi: 10.1038/s41598-019-54903-7.

Giancotti, G., Cancellieri, M., Balboni, A., Giustiniano, M., Novellino, E., Delang, L., Neyts, J., Leyssen, P., Brancale, A., Bassetto, M. 2018 Rational modifications on a benzylidene-acrylohydrazide antiviral scaffold, synthesis and evaluation of bioactivity against Chikungunya virus. European Journal of Medicinal Chemistry, 149, 56-68. doi: 10.1016/j.ejmech.2018.02.054

Ferla, S., Netzler, N., Ferla, S., Veronese, S., Tuipulotu, D., Guccione, S., Brancale, A., White, P., Bassetto, M. 2018 In silico screening for human norovirus antivirals reveals a novel non-nucleoside inhibitor of the viral polymerase. Scientific Reports, 8, 1; doi: 10.1038/s41598-018-22303-y.

Bassetto, M., Leyssen, P., Neyts, J., Yerukhimovich, M., Frick, D., Brancale, A. 2016 Computer-aided identification, synthesis and evaluation of substituted thienopyrimidines as novel inhibitors of HCV replication. European Journal of Medicinal Chemistry, 123, 31-47; doi: 10.1016/j.ejmech.2016.07.035.

PROJECT CONTACT: marcella.bassetto@swansea.ac.uk

Novel anti-cancer agents for combination therapy towards drug-resistant cancers

OVERVIEW: Combination therapy employing drugs with complimentary mechanisms of action is one of the most successful treatment strategies for cancer. Employing novel metallo-drug scaffolds, this project aims to identify candidates that may be combined with FDA-approved DNA damage response (DDR) inhibitors for synergy in drug-resistant or aggressive cancers such as triple-negative breast cancer.

PROJECT OUTCOMES: New synergistic combination therapies for drug-resistant cancers or cancers of unmet need.

AFFILIATED STAFF: Dr Martin Gill

RESEARCH CENTRES/GROUPS: Universiti Putra Malaysia, Malaysia, University of Oxford, UK

PUBLICATIONS:

M. R. Gill, S. N. Harun, S. Halder, R. A. Boghozian, K. Ramadan, H. Ahmad, K. A. Vallis, A ruthenium polypyridyl intercalator stalls DNA replication forks, radiosensitizes human cancer cells and is enhanced by Chk1 inhibition, Sci. Rep., 2016, 6, 31973, N. A. Yusoh, S. W. Leong, S. L. Chia, S. N. Harun, M. B. A. Rahman, K. A. Vallis, M. R. Gill, H. Ahmad, The metallo-intercalator [Ru(dppz)2(PIP)]2+ renders BRCA wild-type triple-negative breast cancer cells hypersensitive to PARP inhibition, ACS Chem Biol, 2020, 15, 378-387

PROJECT CONTACT: m.r.gill@swansea.ac.uk

Impact of non-covalent DNA binders on chromosome stability

OVERVIEW: Non-covalent binding interactions can control DNA structure and functionality and, importantly, these binding interactions are reversible. Of special interest are molecules able to intercalate between DNA base pairs. Contrary to widespread belief, these molecules can stall DNA replication forks without the high levels of genotoxic double-strand damage typically generated by current chemotherapeutics. This project aims to explore the ability of current and new non-covalent DNA binders to achieve specific phenotypes, such as metaphase chromosome misalignment.

PROJECT OUTCOMES: Generating new molecular tools to elucidate the underlying chemical biology of poorly-understood cellular processes.