- Synthesis of novel SN38-aspirin prodrugs for the treatment of hepatocellular carcinoma
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Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. However, there is no effective chemotherapeutic treatment for HCC and its prognosis remains poor. Consequently, it is urgent to find an efficient antitumor agent to treat HCC. In this study, 7-ethyl-10-hydroxycamptothecin (SN38), the bioactive metabolite of the anticancer drug irinotecan (CPT-11), which is 100–1000 times more potent than CPT-11, was coupled with aspirin to give 4 prodrugs. Their structures were characterized by 1 H NMR and elemental analysis. The in vitro anticancer activities of these compounds on two human hepatocellular carcinoma cell lines (BEL-7404 and HepG2) and preliminary mechanisms of action were explored. Our data indicated that these compounds decreased the viability of cancer cell lines in a concentration- and time-dependent manner. Among them, compound 4b significantly inhibited cell viability of HepG2 cells (IC50 = 0.1208 μM) when compared with CPT-11 (IC50 = 18.4267 μM). Furthermore, compound 4b blocked HepG2 cell migration and invasion in vitro. These findings suggest that compound 4b may be used as a promising anticancer agent against HCC.
- Chen, Zhimin,Luo, Yi,Fang, Aiping,Fan, Chen,Zeng, Chenjuan
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- Dabigatran etexilate derivative and pharmaceutical use thereof
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The invention discloses a compound shown as formula (II), a hydrate, isomer, solvate, prodrug or a mixture thereof, and pharmaceutically acceptable salts thereof. The invention also discloses a pharmaceutical composition and a combination preparation containing the compounds as active ingredients, and use of the compounds, the pharmaceutical composition and the combination preparation as thrombininhibitors.
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- Novel conjugates of aspirin with phenolic acid as anti-inflammatory agents having significantly reduced gastrointestinal toxicity
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A series of novel conjugates of aspirin with natural phenolic acid antioxidants connected through a diol linker were designed and synthesized as potential bifunctional agents combining antioxidant and anti-inflammatory activity for reducing gastrointestinal toxicity. In general, the conjugates were found to be efficient antioxidants and many of them demonstrated much more potent anti-inflammatory activity than aspirin. Among them, 5a and 5b which bear the best anti-inflammatory activity exhibited significantly reduced ulcerogenic potency and toxicity compared to aspirin. However, it is evident that the anti-inflammatory activity of these dual-acting molecules in vivo, was not simply consistent with their antioxidant ability in vitro.
- Jiang, Shan,Ding, Ning,Zhang, Wei,Zhang, Yichun,Geng, Meiyu,Li, Yingxia
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p. 215 - 221
(2010/07/05)
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