The College of Pharmacy discussed the MSc thesis entitled “Design, Synthesis, Characterization, Preliminary Biological Evaluation of New Fenoprofen Derivatives” by the student Qasem Abbas Ramadhan and the supervisor, Assistant Professor Dr. Mohammed K. Hadi, at the Pharmaceutical Chemistry Department.
The study aimed to design, prepare new derivatives of fenoprofen, evaluate their antibacterial activity, investigate their binding potential to the bacterial DNA gyrase enzyme using molecular modeling methods.
The study included the preparation of fenoprofen hydrazide, which was used to synthesize a series of N-acyl hydrazone derivatives, sulfonyl hydrazide derivatives, 1,3,4-oxadiazole-2-thiol and its S-alkylated derivatives. The synthesized compounds were characterized using spectroscopic techniques, their antibacterial activity was evaluated against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Streptococcus pneumoniae. Molecular docking, MM-GBSA, molecular dynamics simulations were performed to evaluate the binding of selected compounds to the DNA gyrase enzyme.
The results showed that the successful synthesis, characterization of the targeted derivatives. The synthesized compounds exhibited varying degrees of antibacterial activity. Computational studies supported the binding potential of several derivatives to the DNA gyrase complex, MM-GBSA calculations showed favorable binding energies for some compounds, while molecular dynamics simulations supported the stability of the selected complexes throughout the simulation period.
The study recommends conducting further investigations to determine the structure–activity relationship, evaluate the toxicity, selectivity, pharmacokinetic properties of the most active compounds, expand mechanistic studies and biological experiments to directly verify DNA gyrase inhibition, develop the promising derivatives in future studies.
