The College of Pharmacy discussed the MSc thesis entitled “In silico studies, Synthesis, Characterization and Preliminary Anti-Microbial Evaluation of New Indomethacin Hydrazide Derivatives” by the student yaseen Haleem Hamdoon and his supervisor, Assistant Professor Dr.Mohammed Kamil Hadi, at the pharmaceutical chemistry department.The study aimed to synthesize, characterize, and evaluate the antimicrobial activity of new derivatives of indomethacin hydrazide. The study included compounds that were prepared by modifying the structure of indomethacin using hydrazide reactions with aromatic aldehydes and sulfonyl chloride compounds. The chemical structures of the compounds were confirmed using spectroscopic techniques such as 1H-NMR and ATR-FTIR. The study showed that the final compounds are acceptable and encourage ADMET analyses. Molecular docking showed good interactions with the target protein using cocrystal and ciprofloxacin as a reference ligands. Molecular dynamics simulations (MD Simulation) were performed using GROMACS software to study the compounds’ stability within the target protein’s active site. The RMSD analysis results showed that compound IIIe was stable during the simulation while retaining its key interactions within the protein’s active site. H-bond analysis showed that the compound could form stable hydrogen bonds with important amino acid residues, and PCA analysis showed that the binding of compound IIIe reduced the flexibility of the protein, indicating a higher stability than the free state. This supports its efficacy as a promising antimicrobial. The antimicrobial activity of the compounds was evaluated against several bacterial and fungal strains, such as Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, Streptococcus pyogenes, and Candida albicans, using MIC and inhibition zone. Overall, the results confirmed that compound IIIe is most effective against Gram-positive and Gram-negative bacteria and fungi, with a clear stability within the target protein, making it a strong candidate for developing new antimicrobials. The study recommended assessing other biological activities with anticancer and anti-inflammatory of new derivatives.
