Abstract
While studies have demonstrated the therapeutic potential of triptolide for different cancers including hepatocellular carcinoma (HCC), its development is greatly hurdled by lacking tumor targeting and poor solubility. To address these issues, triptolide was bonded to different site of glucose/glucose analogues via different linkage resulting in triptolide glycoconjugates, which were evaluated with several of xenograft HCC models. Our studies indicated that triptolide linked to the C-6 OH of glucose has better anti-HCC activity with minimal toxicity, which was exampled by conjugate 3. 3 significantly reverses tumor growth in GLUT1 overexpressed xenograft HCC models; it also doses dependently decreases tumor burden and reduce tumor lung metastasis in a highly metastatic orthotopic HCC model, as well increases the survival rate of tumor burdening mice. The present study sheds light on the understanding of the relationship between the structural of glycoconjugates and selective delivery of toxic drug to tumor overexpressing of GLUTs such as HCC.
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Xue, J., Pan, F., Long, T. et al. Glycosylated triptolide affords a potent in vivo therapeutic activity to hepatocellular carcinoma in mouse model. Med Chem Res 32, 254–270 (2023). https://doi.org/10.1007/s00044-022-03008-4
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DOI: https://doi.org/10.1007/s00044-022-03008-4