A Glucose-Triptolide Conjugate Selectively Targets Cancer Cells under Hypoxia

A Glucose-Triptolide Conjugate Selectively Targets Cancer Cells under Hypoxia

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Summary: A major hurdle in the treatment of cancer is chemoresistance induced under hypoxia that is Course a pied - Homme - Vetements - Short - 7" characteristic of tumor microenvironment.Triptolide, a potent inhibitor of eukaryotic transcription, possesses potent antitumor activity.However, its clinical potential has been limited by toxicity and water solubility.To address those limitations of triptolide, we designed and synthesized glucose-triptolide conjugates (glutriptolides) and demonstrated their antitumor activity in vitro and in vivo.Herein, we identified a lead, glutriptolide-2 with an altered linker structure.

Glutriptolide-2 possessed improved stability in human serum, greater selectivity toward cancer over normal cells, and increased potency against cancer Frozen cells.Glutriptolide-2 exhibits sustained antitumor activity, prolonging survival in a prostate cancer metastasis animal model.Importantly, we found that glutriptolide-2 was more potent against cancer cells under hypoxia than normoxia.Together, this work provides an attractive glutriptolide drug lead and suggests a viable strategy to overcome chemoresistance through conjugation of cytotoxic agents to glucose.