Short Report by Dr. Wilma Neumann: BIOLOGICAL EVALUATION OF CARBORANE-CONTAINING COX INHIBITORS at Vanderbilt University (SEPT 09 – SEPT 19)
written by Wilma Neumann (postdoctoral associate at Leipzig University): Over the last years, the groups of Prof. Evamarie Hey-Hawkins (Institute of Inorganic Chemistry, Leipzig University) and Prof. Larry Marnett (Department of Biochemistry, Vanderbilt University School of Medicine) have developed a very fruitful collaboration, supported by the Leipzig-Vanderbilt collaboration project. Recently, we described a very potent and selective inhibitor of cyclooxygenase-2 (COX-2), a carborane-containing indomethacin analogue, which exhibits a novel binding mode in the COX enzyme pocket (W. Neumann, S. Xu, M. B. Sárosi, M. S. Scholz, B. C. Crews, K. Ghebreselasie, S. Banerjee, L. J. Marnett, E. Hey-Hawkins, ChemMedChem 2015, DOI: 10.1002/cmdc.201500199).
In September 2015, I returned to Vanderbilt to continue the biological evaluation of this promising inhibitor and conducted further experiments together with the very supportive co-workers of Larry Marnett. Besides the indomethacin derivatives, we evaluated a new class of carborane-containing COX inhibitors, extending our studies on the potential of the inorganic boron clusters which offer several unique properties for their application as pharmacophores. During my stay at Vanderbilt, I furthermore intensified our collaboration with Prof. Roger Cone (Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine), which also includes application of the versatile carborane clusters. After this inspiring week at Vanderbilt with insights into further techniques and new promising results, I presented the results of our collaborative research projects on carborane-containing COX inhibitors as well as the conjugation of COX inhibitors with platinum-based anti-tumour drugs at the Massachusetts Institute of Technology in Cambridge/MA.
My thanks go to the Leipzig-Vanderbilt collaboration project, supporting this as well as my former visits to Vanderbilt, which intensively promoted our collaborative projects with the Marnett group. I am also very thankful to Larry Marnett for hosting me again, and to his co-workers, especially Brenda Crews, Kebreab Ghebreselasie, Cristina Daniel and Philip Kingsley, performing the biological assays.