2020/09/01 by Emmanuel Datan, Il Minn, Peng Xu +5 · 1 citation
Biochemistry, Genetics and Molecular Biology · Chemistry · Mathematics · Medicine · #ATP Synthase and ATPases Research #Apoptosis #Biochemistry #Biology #Bioorganic chemistry #Cancer #Cancer cell #Cancer therapy #Cell biology #Chemistry #Conjugate #Genetics #Histone Deacetylase Inhibitors Research #Hypoxia (environmental) #Mathematics #Natural Compounds in Disease Treatment #Organic chemistry #Oxygen #Triptolide
paper · pdf · doi:10.1016/j.isci.2020.101536
openalex publication_date 2020/09/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
A major hurdle in the treatment of cancer is chemoresistance induced under hypoxia that is 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 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.