The Official Journal of Asian Association of Schools of Pharmacy
 
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Isoindole-1,3-dione-based a,?-diketo acid bioisosteres as hepatitis C virus NS5B polymerase inhibitors
Ravindra Ramesh Deore, Ajit Dhananjay Jagtap, Pei-Teh Chang, WirunyaTrimethasil and Ji-Wang Chern
Integration of 2-N-hydroxyl- and 2-N-benzoyl-1,3- diketo acid moieties into isoindole-1,3-dione led to the development of two series of hepatitis C virus NS5B polymerase inhibitors. Structural optimization to translate enzyme inhibitory activity to cellular cytotoxicity yielded compound 16c, a moderate enzyme inhibitor (IC50 = 27.3 ÁM) with selective toxicity to hepatitis C virus 1b replicon-containing Ava5 cells (EC50 = 18.0 ÁM). Binding experiments indicated that 16c (Kd = 1.25 ÁM) not only competed with fluorescein-labeled GTP for NS5B binding, but also displaced bound GTP from the polymerase active site.
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Other in Vol. 1 No. 4
Cancer cachexia and metabolism:a challenge in nutrition oncology
How to help first-year pharmacy students to gain the big picture
Fabrication of calcium pectinate microparticles from pomelo pectin by ionotropic gelation
Isoindole-1,3-dione-based a,?-diketo acid bioisosteres as hepatitis C virus NS5B polymerase inhibitors
Chlorpheniramine attenuated hypertensive effect of phenylpropanolamine in rats
 
 


 
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