Medicinal and Bio-nano Chemistry

Research

The Medicinal and Bio-nano research cluster impacts many important areas such as the development of new drugs to treat malaria, TB, filariasis and cancer and the formation of nanomedicines for chronic diseases such as HIV and TB.  Recently the group has also expanded into medicinal chemistry programmes focused on chronic pain and pancreatitis.

Electrostatic potential of active anti-tuberculosis compound

 

 

 

 

 Electrostatic potential of active anti-tuberculosis compound

The Liverpool Medicinal and Bio-nano Chemistry cluster has made a range of important contributions during the assessment period including understanding the mechanisms of drug-action of the 4-aminoquinoline, quinolone and peroxide-based antimalarials  and providing the options for the world’s first orally-dosed HIV nanomedicine therapies. Research projects across the cluster operate at all levels of the drug discovery pipeline, including clinical trials in humans (Isoquine, Phase 1 with GSK/ Medicines for Malaria Venture (MMV) 2008; HIV nanomedicines with the Clinton Health Access Initiative (CHAI) and St Stephen’s AIDS Trust planned for 2014 - ACIE 2010, PNAS 2012, JMC 2009, Adv Healthcare Materials 2013). In total, three of our projects have contributed to the portfolio of the MMV, the largest portfolio of antimalarial drugs developed. The cluster has also identified the first class of inhibitor to inhibit the malaria enzyme PfNDH2, identified orally active quinolones in collaboration with MMV (PNAS 2012, JMC 2012a,b,c) and identified important metabolic interactions of current pharmaceutical excipients that were previously considered inactive (Mol Pharm 2013).  New materials such as hyperbranched polydendrons, multi-functional organic nanomaterials (Adv. Funct. Mat. 2012) and new approaches to solid drug nanoparticles (Nature Nano. 2008) have also underpinned research funding and external collaborations. Strong interactions with large and small companies, hospitals and charities including IOTA NanoSolutions, Pfizer, AstraZeneca, Gilead, Cipla, Abbott and Merck, Médecins Sans Frontières, Clinton Health Access Initiative, St Stephen’s AIDS Trust, British Society for Antimicrobial Chemotherapy, Fight for Sight, Liverpool Health Partners and the Drugs for Neglected Diseases initiative has led to considerable support for research across the cluster with government funding coming from EPSRC, MRC and NIH(US). Collectively, the cluster has published 30 patents during the assessment period, both UoL and collaborative filings with industry.

 

Potent novel insecticide docked into the binding site of the Na channelPotent novel insecticide docked into the binding site of the Na channel

 

 

 

 

 

 

Currently we have active projects in the following research areas:

  • Drug-design, medicinal chemistry of antimalarial, anti-TB, antifilarial , Cyclophilin D targeted small molecules for pancreatitis and allosteric modulators of alpha 1-glycine receptors for chronic pain (O’Neill, Berry)
  • Synthesis of novel nucleic acids analogues as potential therapeutic agents and as mechanistic probes in chemical biology (Cosstick)
  • Chemical biology, design and synthesis of inhibitors of protein-protein interactions, biocatalysis and Proteomics using Click Chemistry Approaches (Carnell, Berry, O’Neill)
  • Transition-metal catalyzed reactions, total synthesis of natural products (O’Neil, Aissa)
  • Molecular modelling in the fields of molecular design, reaction mechanisms and chemoinformatics (Berry)
  • Polyfunctionalised quinuclidines: Designer Ligands for Synthetic Chemistry (O’Neil)
  • Developing Greener catalytic methods for synthesis of chiral intermediates (Xiao).