The College of Pharmacy discussed the MSc thesis entitled “Molecular Modeling, Synthesis, and Preliminary Antiproliferative Activity of 1,2,4-Triazole-Schiff Base Derivatives as Histone Deacetylase Inhibitors” by the student Zaid Mahmood Mohammed and the supervisor, Assistant Professor Dr. Ayad Abed Ali Al-Hamashi, at the Pharmaceutical Chemistry Department.The study aimed to design compounds that inhibit the histone deacetylase enzyme virtually by molecular modeling software’s chemical synthesis of these compounds by the proper organic synthesis method, and in vitro cytotoxic evaluation has been made up by the MTT assay. The study included amide bond formation between the starting material of 4-formylbenzoic acid and 3-amino-1,2,4-triazole using the coupling reagents (EDC-HCl, DMAP, and HOBt), followed by a Schiff base reaction between the produced aldehyde intermediate and various substituted anilines to afford the final compounds. The results showed that compounds K1, K2, and K5 showed comparable antiproliferative activity with vorinostat against HeLa cells. Most interestingly, compound K5 showed higher antiproliferative activity against A549 lung cancer cells, comparable to vorinostat, the drug that is approved for the treatment of these malignancies. The study recommended evaluating the pharmacokinetic properties of the triazole derivatives to overcome the major drawbacks associated with HDACi, such as solubility and bioavailability. In vivo studies on animal models might be conducted to validate the antiproliferative activity of the most active compound.
