The natural product pinnaic acid was isolated from the bivalve Pinna Muricata approximately 25 years ago and was found to be a potent inhibitor of cPLA2, which is an enzyme involved in the inflammatory response pathway. The natural product halichlorine was discovered just prior to pinnaic acid and was found to be a potent inhibitor of VCAM-1 which is also an enzyme linked to inflammatory disease. Furthermore, VCAM-1 has also been shown to play a role during the metatastic phase of cancerous cells. Pinnaic acid and halichlorine have an almost identical structure with both possessing the same 3-dimensional azaspirocyclic core, incorporating five chiral centres each. The unique 3-dimensional structure of these compounds coupled with their proven biological activity make them ideal for further study as drug target candidates in the development of treatments for conditions such as non cardiovascular inflammatory diseases,atherosclerosis and cancer. The aim of this project is to synthesise the azaspirocyclic core of pinnaic acid via an established route, followed by the further functionalisation of the molecule utilising combinatorial chemistry methods, resulting in an analogue library that may be screened for bioactivity. A number of novel compounds have been synthesised and are currently being tested for bioactivity against two cancer cell lines. Further synthetic work is ongoing and resulting compounds will be tested for bioactivity shortly.
Following a successful career as a property insurance underwriter spanning 20 years, I decided I wanted to pursue a second career in the chemical sciences so I returned to education to study chemistry full time. I graduated from Kingston University in 2013 and then undertook a research masters degree at UCL, in preparation for PhD research. I graduated from UCL in 2014 and began my current PhD research position in 2017.