A Lecturer from the Department of Chemistry Publishes a Global Study on the Synthesis, Biological Screening, and Molecular Docking of Drug-carrier Maleimide Derivatives
A Lecturer from the Department of Chemistry Publishes a Global Study on the Synthesis, Biological Screening, and Molecular Docking of Drug-carrier Maleimide Derivatives
Lecturer Dr. Ammar Abdul Hussein Al-Karaawi from the Department of Chemistry published a scientific study titled “Synthesis, Biological Screening, and Molecular Docking of Drug Carrier Maleimide Derivatives” in the Russian Journal of Bioorganic Chemistry. The study aimed to synthesize new maleimide-drug derivatives (Ia-Ic) and test them for their anticancer activity against the MCF-7 cell line and against bacteria (Escherichia coli and Staphylococcus aureus). The prepared compounds were characterized using NMR, C-terminal mass spectrometry, and Fourier transform infrared spectroscopy. The research also included the synthesis of maleimide-drug derivatives (Ia-Ic) by reacting 3-aminobenzoic acid and maleic anhydride in acetone to produce 3-[3-carboxyacrylamido]-benzoic acid, and cyclodehydration of 3-[3-carboxyacrylamido]-benzoic acid using acetic anhydride and sodium acetate as cyclodehydrating agents. The resulting 3-maleimide benzoic acid was converted to an acidic chloride derivative by reaction with thionyl chloride. The 3-[2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl]-benzoyl chloride was then treated with three different amine-containing drugs (4-aminoantipyrine, theophylline, and mesalazine) in the presence of triethylamine (TEA) as a catalyst in dimethylacetamide. The study found that compound (Ic) exhibited high cytotoxicity with an IC50 value of 6.12 μg/ml and demonstrated a high inhibition zone for both selected bacteria, while compounds (Ia) and (Ib) exhibited reasonable cytotoxicity with IC50 values of 26.078 and 22.019 μg/ml, respectively, against MCF7 cells. Molecular docking modeling was performed on the binding sites of two proteins: human 3-alpha-hydroxysteroid dehydrogenase type 3 (PDB ID: 4XO7) and estrogen receptor alpha (ER alpha-E) (PDB ID: 6WOK). Conclusions: We suggest that all compounds have a higher inhibition capacity for the 4XO7 receptor compared to the 6WOK receptor, the predominant receptor in breast cancer. The small binding energies and numerous hydrogen bonds obtained through molecular docking modeling suggest that maleimide derivatives may be effective anti-breast cancer agents.
