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    In Silico and In Vitro Perspectives on the Potential Anticancer Activity and Toxicity of Anticancer Drug Modified with Carbohydrates Containing Novel Triazole Compounds
    (Wiley-V C H Verlag Gmbh, 2025) Gokmen, Buse; Guler, Cem; Sanci, Ebru; Demir, Ramiz; Karayildirim, Cinel Koksal; Alsakini, Karrar Ali Mohammed Hasan; Nalbantsoy, Ayse
    5-Fluorouracil (5-FU) is one of the first-line chemotherapeutic agents used in systemic therapy of solid tumors. However, several challenges restrict the use of 5-FU such as serious side effects and short plasma half-life. Because carbohydrates and 1,2,3-triazoles have various biological activities, they have been extensively used in medicine to obtain more effective anticancer drugs in recent years. The aim of this study is to modify 5-FU with carbohydrates containing 1,2,3-triazole compounds to reduce its toxic effect, and to reveal the anticancer properties of the obtained 5-FU derivatives. These derivatives (5-FU-I, 5-FU-II, and 5-FU-III) revealed dose-dependent cytotoxic effects on CaCo-2, PANC-1, and A549 cancer cells. It was determined that cytotoxic effects of the 5-FUs change dependent on used carbohydrate types, cell lines, and administered doses. These derivatives showed apoptotic and necrotic cell deaths which used to destroy the cancer cells. 5-FUs showed no genotoxic effect in the bacterial reverse mutasyon assay. They demonstrated strong antiangiogenic properties in the HET-CAM test. In silico study results demonstrated that carbohydrate modification can increase half-life and clearance, also decrease side effects of 5-FU. In silico data supported the in vitro findings and results demonstrated 5-FU derivatives were better drug candidates. Our results reveal that 5-FUs derivatives modified carbohydrates containing 1,2,3-triazole compounds have potential in cancer therapy.
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    Tetrachloromethane Induced Acute Liver Injury in Mice: Biochemical and Histopathological Study of the Hepatoprotective Effect of Hep-X Standardized Botanical Dietary Supplement
    (Springer, 2023) Karayildirim, Cinel Koksal; Guner, Adem; Yigitturk, Gurkan; Ince, Iskender; Yasar, Mustafa; Yavasoglu, Nefise Ulku Karabay; Yavasoglu, Altug
    This work was aimed at investigating the hepatoprotective effect of Hep-X, a polyherbal formulation containing Silybum marianum L. (Milk thistle), Rosmarinus officinalis L. (Rosemary), Curcuma longa L. (Turmeric) and Fumaria officinalis L. (Fumitory) as standardized botanical dietary supplement, on mice with CCl4-induced acute liver injury. The total phenolic and flavonoid contents of Hep-X were determined as 0.125 and 0.528 mg/mL, respectively. The quercetin content was determined as 50 mu g/mL using HPLC analysis. The total antioxidant capacity showed correlation between the Hep-X concentration and percentage inhibition of free radicals. Hep-X was administered orally at 25, 50 and 100 mg/kg b.w./day against CCl4-induced hepatotoxicity in mice. The hepatic damage was measured using blood biochemical parameters. Animals upon Hep-X treatment exhibited better drug effIcacy in certain blood parameters than silymarin-treated mice. Also, Hep-X administration significantly ameliorated the liver damage by suppressing iNOS expression and apoptosis as well as by recovery of the histological structure. The obtained results suggest that Hep-X is able to significantly alleviate the hepatotoxicity induced by CCl4 in mice, which can be due to antioxidant properties of the polyherbal formulation.