MyJournals Home  

RSS FeedsMolecules, Vol. 24, Pages 3675: Discovery of Novel Integrase Inhibitors Acting outside the Active Site Through High-Throughput Screening (Molecules)

 
 

12 october 2019 17:04:41

 
Molecules, Vol. 24, Pages 3675: Discovery of Novel Integrase Inhibitors Acting outside the Active Site Through High-Throughput Screening (Molecules)
 




Currently, an increasing number of drugs are becoming available to clinics for the treatment of HIV infection. Even if this targeted therapy is highly effective at suppressing viral replication, caregivers are facing growing therapeutic failures in patients, due to resistance with or without treatment adherence concerns. Accordingly, it is important to continue to discover small molecules that have a novel mechanism of inhibition. In this work, HIV integrase inhibitors were selected by high-throughput screening. Chemical structure comparisons enabled the identification of stilbene disulfonic acids as a potential new chemotype. Biochemical characterization of the lead compound stilbenavir (NSC34931) and a few derivatives was performed. Stilbene disulfonic acid derivatives exhibit low to sub-micromolar antiviral activity, and they inhibit integrase through DNA-binding inhibition. They probably bind to the C-terminal domain of integrase, in the cavity normally occupied by the noncleaved strand of the viral DNA substrate. Because of this original mode of action compared to active site strand transfer inhibitors, they do not exhibit cross-resistance to the three main resistance pathways to integrase inhibitors (G140S-Q148H, N155H, and Y143R). Further structure–activity optimization should enable the development of more active and less toxic derivatives with potential clinical relevance.


Del.icio.us Digg Facebook Google StumbleUpon Twitter
 
30 viewsCategory: Biochemistry, Chemistry, Molecular Biology
 
Molecules, Vol. 24, Pages 3676: Synthesis and Evaluation of Pyrimidine Steroids as Antiproliferative Agents (Molecules)
Molecules, Vol. 24, Pages 3673: Cinnamil- and Quinoxaline-Derivative Indicator Dyes for Detecting Volatile Amines in Fish Spoilage (Molecules)
 
 
blog comments powered by Disqus


MyJournals.org
The latest issues of all your favorite science journals on one page

Username:
Password:

Register | Retrieve

Search:

Molecular Biology

Use these buttons to bookmark us:
Del.icio.us Digg Facebook Google StumbleUpon Twitter


Valid HTML 4.01 Transitional
Copyright © 2008 - 2019 Indigonet Services B.V.. Contact: Tim Hulsen. Read here our privacy notice.
Other websites of Indigonet Services B.V.: Nieuws Vacatures News Tweets Travel Photos Nachrichten Indigonet Finances Leer Mandarijn