Matteo Antonio Scrugli
Inhibitory effect of 2,3,5,6-tetrafluoro-4-[4-(Aryl)-1H-1,2,3-triazol-1-yl]benzenesulfonamide derivatives on HIV reverse transcriptase associated rnase H activities
ESPOSITO, FRANCESCA;CORONA, ANGELA;GRANDI, NICOLE;TRAMONTANO, ENZO;
2016-01-01
Abstract
The HIV-1 ribonuclease H (RNase H) function of the reverse transcriptase (RT) enzyme catalyzes the selective hydrolysis of the RNA strand of the RNA:DNA heteroduplex replication intermediate, and represents a suitable target for drug development. A particularly attractive approach is constituted by the interference with the RNase H metal-dependent catalytic activity, which resides in the active site located at the C-terminus p66 subunit of RT. Herein, we report results of an in-house screening campaign that allowed us to identify 4-[4-(aryl)-1H-1,2,3-triazol-1-yl]benzenesulfonamides, prepared by the “click chemistry” approach, as novel potential HIV-1 RNase H inhibitors. Three compounds (9d, 10c, and 10d) demonstrated a selective inhibitory activity against the HIV-1 RNase H enzyme at micromolar concentrations. Drug-likeness, predicted by the calculation of a panel of physicochemical and ADME properties, putative binding modes for the active compounds, assessed by computational molecular docking, as well as a mechanistic hypothesis for this novel chemotype are reported.File | Dimensione | Formato | |
---|---|---|---|
Pala et al ijms 2016.pdf accesso aperto
Descrizione: Articolo principale
Tipologia: versione editoriale
Dimensione 1.97 MB
Formato Adobe PDF
|
1.97 MB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.