Since 1993 as a direct consequence of our work on the Xylariaceous Fungi some members of my group have worked on collaborative projects with colleagues in the Institute of Cancer Therapeutics at Bradford.
We have evaluated the possible use of the naturally occuring cytochalasins, secondary metabolites from members of the Fungus Genus Xylaria (see example structure in Header to this Web Site), as anti-cancer agents. The toxicities of 18 cytochalasins on 8 cell lines have been determined. The effect of the length of the exposure time of the cells to the drugs has also been looked at. The effects of different structural features on the relative toxicities of the 18 drugs in vitro have been evaluated. Some have also been evaluated for activity in vivo. We have also worked on the selective chemical modification of naturally occuring cytochalasins and evaluated the effect of these changes on anti-cancer activity in vitro. The results of our studies suggest that these compounds act as actin binding agents and that they merit further investigation as potential drugs for the treatment of breast and ovarian cancers.
Research Students - Ioana Popa (1993-96) and Steven Coombes (1997-2000)
In collaboration with Dr Roger Phillips of the Tom Connors Cancer Research Centre funding, £29,586, was secured from the Association for International Cancer Research to support work (1997-9) on the synthesis and evaluation of DT-Diaphorase activated bioreductive drugs. Again the project lead compound is related to a natural product isolated from a fungus. We are now preparing and evaluating synthetic analogues in order to develop a possible drug.
Research Students - Gill Steans (1996-99), Charlotte Catignani (1999-2002), Tariq Mahmood 2006-2009.
The isolation and structure determination by multinuclear NMR spectroscopy (and other spectroscopic techniques) of secondary metabolites from Xylariaceous Fungi grown in culture. This is a collaboative project with Dr R L Edwards at Bradford and a mycologist, Professor A J S Whalley, at Liverpool John Moores University. We have established an international reputation for our work in this area. Since 1991 several research students have worked at Bradford on this topic. These fungi are a rich source of novel natural products of possible pharmaceutical interest.
Research Students - Moni O. Adeboya (1991-94), Claire L. Oliver (1993-96), Hai-Ho Nguyen-Nygoc (1994-97), Zhenping Ni [Sandy Johnson] (1996-98), Pattama Pittayakhajonwut (1995-99), Parisa Sarkhail (2004-5), Emmanuel Oppong (2004-7), Harith Al-Busaidi (2007-10). Rwaida Al-Haidari (2008-11).
In a collaborative venture with Dr Amani Awaad , Professor of Pharmacognosy, Chemistry Department - Faculty of Sciences - King Saud University, Riyadh, KSA, Natural Products isolated from Medicinal Plants are being screened for pharmacological activity and the structures of isolated compounds determined.
The future
Natural product work will continue hand-in-hand with the anti-cancer drug synthesis work, since if it were not for the former the latter would not now be a reality. The future looks exciting.
In this collaborative project with Professor C Heron of Archaelogical Sciences samples recovered from the medicine chest of a Barber-Surgeon from the Tudor Warship, The Mary Rose, were examined by scientific methods (GLC, GC-Mass Spec, IR, NMR etc).
Research Student - Brendan Derham (1996-99)