The Faculty of Pharmacy discussed the MSc thesis entitled “Design, Synthesis, and Biological Evaluation of Novel N-Hydroxyurea Derivatives as Possible Dual HDAC/BET Inhibitors” by Hayjaa Mohesen Mousa and her supervisor, Assistant Professor Dr. Ayad Abed Ali Al-Hamashi in the Pharmaceutical Chemistry Department. The study aimed to design new N-hydroxyurea-based potential histone deacetylase (HDAC) inhibitors that were docked against different isoforms using the Schrodinger modeling suite. Compounds with the N-hydroxyurea moiety were linked to the cap and linker to give the final compounds that showed virtual bidentate zinc chelation in the HDACs active site, which is important for the inhibition. Compounds containing urea hydroxylates as a linking group for zinc were manufactured, and zinc is considered important in inhibiting the activity of the histone deacetylase enzyme. The reactions were monitored using thin-layer chromatography to ensure the completion of the reactions, and the compounds were purified using column chromatography and Combiflash. The final compounds were characterized using IR spectroscopy and NMR spectroscopy, and the results showed good agreement with the synthesized compounds. An evaluation of preliminary antiproliferative activities against colon cancer cell lines showed that the compounds with N-hydroxyurea molecules showed superior colon cancer cell line (LS-174T) growth inhibition efficacy compared to the FDA-approved HDAC inhibitor Vorinostat.
