In Silico and In Vitro Perspectives on the Potential Anticancer Activity and Toxicity of Anticancer Drug Modified with Carbohydrates Containing Novel Triazole Compounds

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.