- Synthesis of Fluorophores that Target Small Molecules to the Endoplasmic Reticulum of Living Mammalian Cells
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The endoplasmic reticulum (ER) plays critical roles in the processing of secreted and transmembrane proteins. To deliver small molecules to this organelle, we synthesized fluorinated hydrophobic analogues of the fluorophore rhodol. These cell-permeable fluorophores are exceptionally bright, with quantum yields of around 0.8, and they were found to specifically accumulate in the ER of living HeLa cells, as imaged by confocal laser scanning microscopy. To target a biological pathway controlled by the ER, we linked a fluorinated hydrophobic rhodol to 5-nitrofuran-2-acrylaldehyde. In contrast to an untargeted nitrofuran warhead, delivery of this electrophilic nitrofuran to the ER by the rhodol resulted in cytotoxicity comparable to the ER-targeted cytotoxin eeyarestatin I, and specifically inhibited protein processing by the ubiquitin-proteasome system. Fluorinated hydrophobic rhodols are outstanding fluorophores that enable the delivery of small molecules for targeting ER-associated proteins and pathways.
- Meinig, J. Matthew,Fu, Liqiang,Peterson, Blake R.
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- Eeyarestatin I derivatives with improved aqueous solubility
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Inhibition of p97 (also known as valosin-containing protein (VCP)), has been validated as a promising strategy for cancer therapy. Eeyarestatin I (EerI) blocks p97 through a novel mechanism of action and has favorable anti-cancer activities against cultured cancer cells. However, its poor aqueous solubility severely limits its in vivo applications. To circumvent this problem, we have identified EerI derivatives that possess improved aqueous solubility by introducing a single solubilizing group. These modified compounds preserved endoplasmic reticulum (ER) stress-inducing and antiproliferative activities as well as generally good in vitro metabolic properties, suggesting that these EerI derivatives could serve as candidates for further optimization.
- Ding, Rui,Zhang, Ting,Xie, Jiashu,Williams, Jessica,Ye, Yihong,Chen, Liqiang
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- Synthesis and in vitro antibacterial activities of novel oxazolidinones
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Design and synthesis of novel piperazinylaryloxazolidinones possessing heteroaryl groups are described and their in vitro antibacterial activities have been evaluated by MIC assay. Compounds (S)-N-[3-{3-fluoro-4-[4-[3-(5-nitrofuran-2-yl)-acryloyl]-piperazin-1-yl] -phenyl}-2-oxo-oxazolidin-5-yl-methyl] acetamide (6o), (S)-N-[3-{3-fluoro-4-[4-[3-(5-nitrothien-2-yl)-acryloyl]-piperazin-1-yl] -phenyl}-2-oxo-oxazolidin-5-yl-methyl] acetamide (6p) and N-oxide of (S)-N-[3-{3-fluoro-4-[4-[3-(5-nitrofuran-2-yl)-acryloyl]-piperazin-1-yl] -phenyl}-2-oxo-oxazolidin-5-yl-methyl] acetamide (9) showed superior antibacterial activities than linezolid and also active against the linezolid resistant Staphylococcus aureus strains.
- Srivastava, Brijesh Kumar,Jain, Mukul R.,Solanki, Manish,Soni, Rina,Valani, Darshan,Gupta, Sunil,Mishra, Bhupendra,Takale, Vijay,Kapadnis, Prashant,Patel, Harilal,Pandya, Purvi,Patel, Jayendra Z.,Patel, Pankaj R.
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p. 683 - 693
(2008/09/20)
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- Process for the production of β-(5-nitro-2-furyl)-acrolein
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An improved process for the production of β-(5-nitro-2-furyl)-acrolein by reacting 5-nitro-furfural and acetaldehyde in the presence of a secondary amine, the improvement comprises effecting the reaction in an aliphatic carboxylic acid of 2 to 4 carbon atoms.
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