1623784-75-7Relevant articles and documents
Design, synthesis, and biological evaluation of 1,3-diarylpropenones as dual inhibitors of HIV-1 reverse transcriptase
Meleddu, Rita,Cannas, Valeria,Distinto, Simona,Sarais, Giorgia,Del Vecchio, Claudia,Esposito, Francesca,Bianco, Giulia,Corona, Angela,Cottiglia, Filippo,Alcaro, Stefano,Parolin, Cristina,Artese, Anna,Scalise, Daniela,Fresta, Massimo,Arridu, Antonella,Ortuso, Francesco,Maccioni, Elias,Tramontano, Enzo
supporting information, p. 1869 - 1879 (2014/08/18)
A small library of 1,3-diarylpropenones was designed and synthesized as dual inhibitors of both HIV-1 reverse transcriptase (RT) DNA polymerase (DP) and ribonuclease H (RNase H) associated functions. Compounds were assayed on these enzyme activities, which highlighted dual inhibition properties in the low-micromolar range. Interestingly, mutations in the non-nucleoside RT inhibitor binding pocket strongly affected RNase H inhibition by the propenone derivatives without decreasing their capacity to inhibit DP activity, which suggests long-range RT structural effects. Biochemical and computational studies indicated that the propenone derivatives bind two different interdependent allosteric pockets.
