Medway school of pharmacy

Dr Casely-Hayford obtained his BSc with first class honours in Pharmaceutical Chemistry from Queen Mary, University of London in 2000. He then joined the School of Pharmacy, University of London to study for a PhD in Medicinal Chemistry focusing on the chemical synthesis and biological evaluation of potential anti-cancer agents based on the azinomycins. This work resulted in several publications and the filing of one patent. Prior to joining Medway School of Pharmacy as a lecturer in Pharmaceutical Chemistry, he was a Post Doctoral Research Fellow at the London School of Pharmacy. His expertise is in pharmaceutical chemistry, synthetic organic chemistry, peptide synthesis, organic medicinal chemistry and drug DNA interactions.

Dr Casely-Hayford teaches on the MPharm and Foundation Degree Programmes. He is course leader for one MPharm course (Medicines Design and Manufacture 1, MP1) and one Foundation Degree course (Essential Chemistry for Pharmacy 1, C1).

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The main theme of Dr Casely-Hayford’s research group is the use of natural products as lead compounds for the design, synthesis and discovery of novel analogues with better biological activity and selectivity as potential cancer therapeutics. Current efforts are directed towards the following areas:

Design, synthesis and biological evaluation of natural product analogues

The cryptophycin family of antitumour-antibiotics were isolated from the blue-green algae Nostoc sp. in the event of screening over 1000 blue-green algae for tumour activity. They are a potent and strongly tumour-selective class of tubulin-binding antimitotic agents and show excellent activity against solid tumours which have developed multi-drug resistance (MDR). An analogue of the cryptophycins, cryptophycin 52 was recently withdrawn from phase trials due to severe side effects. Our current work on this compounds include:

• Design and synthesis of a new class of anti-tumour agents based on the cryptophycins
• Development of a solid-phase technique for the rapid synthesis of structural analogues with better therapeutic potential and toxicity profile.
• Development of a pro-drug approach for targeting synthesised analogues to tumour cells.

Other natural products of interest to the group include the dominicin antitumour-antibiotics, artemisinin and the azinomycins.

Studies on the molecular mechanism of antitumour activity

The azinomycin epoxide is a small molecule which forms the left hand portion of the natural product azinomycin A and B which derive their antitumour activity via DNA cross-linking. Although the mono functional azinomycin epoxide cannot cross-link DNA, it maintains potent antitumour activity comparable to the clinical agent mitomycin C. In collaboration with Dr Vadim Sumbayev, we are investigation the molecular mechanisms leading apoptosis upon treatment with these compounds.

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Selected Recent Publications

• Marie-Helen David-Cordonier, Maxwell Casely-Hayford, Mostafa Kouach, Gilbert Briand, Laurence H. Patterson, Christian Bailly, and Mark Searcy (2006). Stereoselectivity, Sequence Specificity and Mechanism of Action of the Azinomycins Epoxide. ChemBioChem, 7: 1658-1661.
• Casely-Hayford, M. A.; Ortuzar Kerr, N.; Smith, E.; Gibbons, S.; Searcey, M. (2005). Antitumour nntibiotics with potent activity against Multidrug resistant staphylococcus aureus: A new approach to targeting resistant bacteria. Medicinal Chemistry. 1: 619-628.
• Casely-Hayford MA., Pors K., Patterson LH., Hartley JA and Searcey M. (2005). Design and synthesis of a DNA cross-linking analogue. Organic & Biomolecular Chemistry 3 (19): 3585-3589.
• Casely-Hayford MA., Pors K., James CH., Patterson LH., Gerner C., Neidle S and Searcey M. (2005). Truncated azinomycin analogues intercalated into DNA. Bioorganic and Medicinal Chemistry Letters 15: 653-656.
• Casely-Hayford MA and Searcey M (2003). The azinomycins, Discovery, Synthesis, and DNA-binding Studies. In DNA and RNA binders – From small molecules to drugs. Eds. Demeunynck M, Bailly C and Wilson WD. 2: 676 – 696.

Patents

• Mark Searcey, Maxwell Casely-Hayford, Klaus Pors, Laurence H. Patterson. Analogues of the azinomycin as antitumour agents and as prodrugs. British Patent Application number 0505644.5 Filed 18th March 2005.

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