Elucidating the Metabolic and Toxicological Profile of Novel Bisquinoline Anti-Malarials

Every 60 seconds, a child dies of malaria; a preventable and curable disease. This equates to 1,300 children losing their lives every day, due to an infected mosquito bite. With an estimated 207 million cases and 627 000 attributable deaths reported globally during 2012, malaria remains a significant clinical problem primarily affecting our most disadvantaged populations. Inadequate vector control, increasing parasite resistance and poor access to effective therapies has significantly hampered prophylaxis, chemotherapy and disease eradication. Without further intervention and drug development many more lives will be lost to this devastating disease.

We have used a rational drug design approach to develop a promising series of novel bis-quinoline compounds, with preliminary data showing excellent anti-malarial activity in vivo (3 day test) and in resistant parasites (in vitro). This project will begin with the synthesis and spectrophotometric characterisation of the novel compounds for testing, before determining their metabolic fate and toxicity profile. The toxicological characterisation of these bis-quinoline anti-malarials will be explored in vitro using cytotoxicity and biochemical analyses, such as lactate dehydrogenase and glutathione assays, alongside microsomal incubations with liquid chromatography-mass spectrometry to identify metabolites and their stability.

This PhD project is funded through LJMU Faculty of Science and is a collaboration between the Biomedical Science and Medicinal Chemistry and Natural Products Research groups within the School of Pharmacy and Biomolecular Sciences at Liverpool John Moores University. Alonside, Dr Laura Randle, co-supervisors will be Dr Fyaz Ismail and Professor Satya Sarker.
The work will largely take place in newly refurbished state-of-the-art Life Sciences Building. Utilising Dr Randle’s previous experience exploring Isoquine metabolism and Dr Ismail’s medicinal chemistry expertise, the successful candidate will acquire valuable training and knowledge in the skills required to probe and exploit new chemical entities for the treatment of malaria.

The deadline for applications is Friday 30th October 2015 (5pm local time). The student must be enrolled by 31st December 2015.

Applicants should send a CV, two academic references and a personal statement outlining why they are interested in applying for this PhD to Dr Laura Randle (below).
Also, if you have any questions or require further information, please contact Dr Laura Randle by email ([Email Address Removed]) or by phone (0151 231 2533) for an informal chat.

More information about the School of Pharmacy and Biomolecular Sciences at Liverpool John Moores University can be found at https://www.ljmu.ac.uk/about-us/faculties/faculty-of-science/school-of-pharmacy-and-biomolecular-sciences