Design, Synthesis, and Biological Evaluation of 1, 3‐Diarylpropenones as Dual Inhibitors of HIV‐1 Reverse Transcriptase. Issue 8 (21st May 2014)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: ChemMedChem. Volume 9:Issue 8(2014:Aug.)
• Page Start: 1869
• Page End: 1879
• Publication Date: 2014-05-21
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201402015
• Languages: English
• ISSNs: 1860-7179

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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.</p> </abstract>