Dr. John Hadfield
School of Science, Engineering and Environment
Current positions
Senior Lecturer in Medicinal Chemistry
Biography
My first degree was in Chemistry from the University of Nottingham. Following this, I studied for a PhD in Organic Chemistry at Trent Polytechnic. I worked as a Postdoctoral Scientist at the University of Warwick where I investigated the biogenesis of riboflavin.
I was then appointed to a postdoctoral position at the Paterson Institute, Christie Hospital, Manchester where I worked on developing anticancer agents. I was appointed as a Lecturer in Chemistry at the University of Salford in 2001, and Senior Lecturer in 2008
Areas of research
Antivascular agents, Chalcones, Synthesis in water
I teach various topics at Salford: Organic Chemistry L4-6, Pharmaceutical Science, Natural Products Chemistry, Environmental Chemistry, Anticancer drugs, Biosynthesis and Carbohydrate Chemistry.
At the Paterson Institute, I gave seminars and lectures on anticancer drug design. I am Programme Leader for the MScs in Drug Design & Discovery and Biotechnology.
Bio-reductive alkylating agents: These are quinone pro-drugs related to the clinically-trialled RH1, but with a terminal alcohol function protected by an acetyl group. Of particular interest is the quinone pro-drug Es5 which is a potent bio-reductive anticancer agent activated by the enzyme DT-Diaphorase. This enzyme is overexpressed in many tumours. These pro-drugs are converted to active intermediates by enzymatic activity either in hypoxic areas of solid tumours or by increased activity of these enzymes compared with normal tissues and, therefore, should exhibit tumour-selective cytotoxicity.
Two-photon activation: The Z-combretastatins are natural products which exhibit potent, selective antivascular activity to tumours within minutes of administration. Unfortunately, they also show cardiac toxicity. The E-combretastatins do not exhibit antivascular activity and are not cardiotoxic. However, these E-isomers can be converted to their active Z counterparts by treatment with light. This requires two-photon activation using lasers. This research is developing E-isomers which can be administered directly to patients, which are then activated with light. Such a technology would prevent the active Z-isomer from circulating through the heart and eliminate any cardiotoxic events.
Antivascular agents: Other research on antivascular agents involves the development of dibenzoxepines. Preliminary results indicate that these oxepines show similar antivascular potency as the Z-combretastatins. Intriguingly these oxepines show antivascular activity at doses which do not cause cardiotoxicity.
Chalcones: Rhabdomyosarcoma is the third most prevalent children’s cancer and approximately 3% of children’s cancers are rhabdomyosarcomas with 250 US and 60 UK children diagnosed a year. Phenothiazinyl chalcones exhibit cytotoxicity to rhabdomyosarcoma cells and this research programme aims to develop these into clinical agents. Our previous work has shown that specific modifications to the double bond of chalcones can markedly improve their cytotoxicity to cancer cell lines. This project aims to similarly modify the phenothiazinyl derived chalcones and identify a suitable candidate for clinical evaluation as an agent to combat rhabdomyosarcoma.
Green chemistry: The most used methodology for synthesising stilbenes uses Nobel-prize winning Wittig chemistry. This chemistry uses flammable solvents and flammable/pyrophoric bases. We have developed a method which uses water as the solvent and simple, non-flammable bases such as lithium hydroxide and potassium carbonate.
Qualifications
- BSc, Chemistry, University of Nottingham.
- PhD, Organic Chemistry, Trent Polytechnic, Nottingham.
Memberships
- Member of the Royal Society of Chemistry, Chartered Chemist.
- Chairman of Onco-NX (2011-14); presently Scientific Advisor to Incanthera.
- Editorial Board of International Journal of Medical Engineering and Informatics.