The College of Pharmacy discussed the PhD dissertation entitled “In-silico Studies, Synthesis and Cytotoxicity Evaluation of New Anthraquinone-2-Heterocyclic Derivatives” by the student Mazin Nadhim Mousa and the supervisor, Assistant Professor Dr Mohammed Hassan Mohammed, at the Pharmaceutical Chemistry Department.
The study aimed to design and synthesize novel anthraquinone-2-carboxylic acid derivatives linked to heterocyclic rings (1,3,4-oxadiazole, 1,2,4-triazole, and 1,3,4-thiadiazole) and to evaluate their anticancer activity using integrated computational modeling techniques and in vitro biological studies.
The study included the synthesis of a series of fifteen novel anthraquinone-derived hybrid compounds through several chemical steps starting from anthraquinone-2-carboxylic acid. The structures of the synthesized compounds were characterized using infrared spectroscopy (IR), proton and carbon nuclear magnetic resonance spectroscopy (¹H-NMR and ¹³C-NMR), and mass spectrometry. In silico molecular docking and molecular dynamics simulation studies were conducted against PKM2 and Topoisomerase II enzymes. The cytotoxic activity of the compounds was evaluated in vitro using the MTT assay against two cancer cell lines and one normal cell line, followed by flow cytometry analysis to assess apoptosis and cell cycle progression.
The results showed that the synthesized compounds possessed strong and stable binding affinity toward the Topoisomerase enzyme in computational studies. Biological investigations revealed highly selective cytotoxic activity against cancer cells compared to normal cells. Compound T1 exhibited remarkable potency and selectivity against lung cancer cells with an IC50 value of 89.72 µg/mL, while compound O3 showed an IC50 value of 120.6 µg/mL against liver cancer cells. Further analyses confirmed the ability of these compounds to disrupt cell cycle progression and induce apoptosis in cancer cells.
The study recommended conducting further detailed investigations to elucidate the precise molecular and enzymatic mechanisms of action of the promising compounds, optimizing the structural framework of these derivatives to enhance their pharmacological activity and reduce toxicity, and evaluating the most active compounds through in vivo studies using animal models as a preliminary step toward future clinical assessment.
