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    Mechanisms underlying citrinin-induced toxicity via oxidative stress and apoptosis-mediated by mitochondrial-dependent pathway in SH-SY5Y cells
    (Taylor and Francis Ltd., 2022) Abudayyak, Mahmoud; Karaman, Ecem Fatma; Ozden, Sibel
    Citrinin (CIT) is a mycotoxin produced as a secondary product by the generaAspergillus,Penicillium,Monascus,and other strains. CIT has the potential for contaminating animal feed and human food suchas maize, wheat, rye, barley, oats, rice, cheese, and sake. Although CIT is primarily known as a nephro-toxic mycotoxin, it also affects other organs, including the liver and bone marrow, and its mechanisms oftoxicity have not been clearly elucidated. There is a further lack of studies investigating the potential forCIT-induced neurotoxicity and its mechanisms. In the current study, SH-SY5Y human neuroblastoma cellline was treated with CIT for 24 h to evaluate various toxicological endpoints, such as reactive oxygenspecies (ROS) production and apoptosis induction. Results indicate that CIT has an IC50value of250.90lM and cell proliferation decreased significantly at 50 and 100lM CIT concentrations. These sameconcentrations also caused elevated ROS production ( 34.76%), apoptosis ( 9.43-fold) and calcium ionmobilization ( 36.52%) in the cells. Results show a significant decrease in the mitochondrial membranepotential ( 86.8%). We also found that CIT significantly upregulated the expression of some genesrelated to oxidative stress and apoptosis, while downregulating others. These results suggest that apop-tosis and oxidative stress may be involved in the mechanisms underlying CIT-induced neurotoxicity.
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    Synthesis of novel urea and sulfonamide derivatives of isatin schiff bases as potential anti-cancer agents
    (Bentham Science Publishers, 2022) Demirel, Ural Ufuk; Ölgen, Süreyya; Karaman, Ecem Fatma; Tanol, Mehmet; Özden, Sibel; Göker, Hakan
    Background: Among the many types of chemical scaffolds, isatin derivatives, including their Schiff bases, have been extensively studied to find novel therapeutic agents against cancer. Amide or urea groups containing derivatives were also discovered to be tyrosine kinase inhibitors. Objective: This study aims to find potent compounds by designing 16 novel urea and sulfonamide derivatives of isatin Schiff bases. Methods: Compounds were tested against PC-3, HepG2, SH-SY5Y, A549 cancerous, and NIH/3T3 non-cancerous cell lines using cell culture assay. Results: Among the tested compounds 7a, 7b, 7c, 7d, 7h, 8a, and 8f presented potential inhibitions against cellular proliferation activities of HepG2 cells with average IC50 values of 31.97, 42.13, 31.50, 47.98, 32.59, 43.44, and 37.81 µM, respectively. They showed better inhibition potencies than the reference compound doxorubicin, and its value was measured as 51.15 μM in the same culture assay. The cytotoxic activities of the compounds in other cell lines were found to be less potent compared to doxoru-bicin. Conclusion: In vitro experiments demonstrated that designed compounds have the first evidence that they might be active against hepatocellular carcinoma. According to ADME prediction results, all compounds presented drug-like and good metabolic properties.