摘要

Some hydroxamate compounds induce cancer cell death by intracellular reactive oxygen species (ROS). This study introduced the hydroxamate core into lovastatin, a fungus metabolite clinically used for the treatment of hypercholesterolemia. The resulting compounds were evaluated for the activity for inducing ROS production. Most compounds exhibited higher activity than original lovastatin. Of these compounds, compound 3c had the most potent activity. Test of cytotoxicity in a panel of human cancer cell lines indicated compound 3c had activities superior to cisplatin in prostate cancer PC-3 cells and breast cancer T47D cells. In contrast, it in amounts up to 40 μM had a much lower cytotoxic effect on normal human IMR-90 cells. Further profiling of cell cycle progression, cell apoptosis, and DNA damage activated checkpoint signaling pathway revealed the important role of compound 3c-mediated cytotoxicity in ROS generation.
原文英語
頁(從 - 到)5528-5533
頁數6
期刊Bioorganic and Medicinal Chemistry Letters
26
發行號22
DOIs
出版狀態已發佈 - 2016

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

指紋 深入研究「Synthesis and biological evaluation of lovastatin-derived aliphatic hydroxamates that induce reactive oxygen species」主題。共同形成了獨特的指紋。

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