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- W2937763513 abstract "As FDA-approved chemotherapeutic agents, cisplatin, oxaliplatin, and 5-fluorouracil are widely used in clinic but limited by severe side-effects. To ameliorate their respective defects, a series of dual-prodrug by linking oxoplatin and 5-FU were designed and synthesized. The assembled compounds 10-17, named Fuplatin, exhibited much higher cytotoxicity against the tested cancer cells while lower cytotoxicity toward the human normal lung cells than free drugs or their combinations. Among them, 14 enhanced cellular accumulation with 62- and 825-fold amount of oxaliplatin and 8 at 9 h, respectively, significantly induced DNA damage and cell apoptosis, and inhibited migration and invasion in HCT-116 cells. Compound 14 arrested the cell cycle at S and G2 phases and up-regulated thymidylate synthase and p53, consistent with the results of the combination, suggesting 14 adopted a collaborative mode of 5-FU and oxaliplatin to kill cancer cells. In vivo, compound 14 showed high antitumor effect and no observable toxicity in NOD/SCID mice bearing HCT-116 tumors." @default.
- W2937763513 created "2019-04-25" @default.
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- W2937763513 date "2019-04-19" @default.
- W2937763513 modified "2023-09-26" @default.
- W2937763513 title "Fuplatin: An Efficient and Low-Toxic Dual-Prodrug" @default.
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- W2937763513 doi "https://doi.org/10.1021/acs.jmedchem.9b00128" @default.
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