An Endogenous Reactive Oxygen Species (ROS)-Activated Histone Deacetylase Inhibitor Prodrug for Cancer Chemotherapy.
作者： Somnath D. Bhagat , Usha Singh , Ram Kumar Mishra , Aasheesh Srivastava
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摘要: Suberoylanilide hydroxamic acid (SAHA, vorinostat) is a potent small-molecule pan-inhibitor of histone deacetylases (HDACs) approved for treatment cutaneous T-cell lymphoma (CTCL). However, SAHA exhibits poor selectivity cancer cells over noncancer cells. With an aim to improving its cells, we generated novel prodrug (SAHA-OBP) that activated in the presence hydrogen peroxide, reactive oxygen species (ROS) known be overexpressed The high endogenous ROS content triggers rapid removal 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl carbonyl (OBP) cap release active SAHA. SAHA-OBP demonstrates selective activity against multiple cell lines such as HeLa, MCF-7, MDA-MB-231, and B16-F10, while remaining benign toward downstream effects released from induction apoptosis. was also found effective on multicellular tumor spheroids (MCTS). designed this study undergoes ROS-dependent activation imparts much-needed
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