الفهرس | Only 14 pages are availabe for public view |
Abstract Background: Acridine derivatives have garnered significant attention from medicinal chemists due to their diverse range of biological activities, encompassing antifungal, parasitic, antiviral, antibacterial, and anticancer properties. Methods: In this study, eleven compounds were synthesized according to a previously established protocol, and their impact on cell growth inhibition, induction of apoptosis, and cell cycle distribution was assessed in human hepatocellular carcinoma HepG2 cells and human colon cells HCT-116 and breast MF-7. Furthermore, their inhibitory effects on the enzymes topoisomerase (Topo) I and II were investigated in vitro using commercially available DNA kit followed by PCR and gel electrophoresis. Molecular docking studies were conducted to confirm the binding mechanism of these compounds to the enzyme’s active site. Results: Compound 8b demonstrated the highest potency against Topo-I, with an IC50 value of 3.41 µg/ml, while compound 7c displayed a significant inhibitory effect on Topo II, with an IC50 of 7.33 µ/ml, outperforming both the other compounds and the control drug. The efficacy of compounds 7c and 8b against topoisomerases was consistent with their potent anti-proliferative properties, which involved the induction of apoptosis and a reduction in the S phase of the cell cycle. Molecular docking analysis suggested that these two compounds exerted their anti-proliferative and proapoptotic effects primarily through their potent inhibitory action on Topo II, rather than on Topo I. Conclusion: Compounds 7c and 8b hold promise as potential anti-cancer drugs due to their anti-proliferative and proapoptotic effects, which are mediated by their action on the Topoisomerase enzyme, particularly Topo II. |