2-(Trihydroxyphenyl)thienopyrimidinones as Key Scaffolds for Targeting a Novel Allosteric Site of HIV-1 Integrase.

ABSTRACT: A promising novel class of 2-(trihydroxyphenyl)thieno[2,3-d]pyrimidin-4(3H)-ones as HIV-1 integrase (IN) allosteric inhibitors is reported. All compounds were considerably more effective than the control compound LEDGIN-6, showing an inhibitory activity in the low micromolar range in both the HIV-1 integrase LEDGF/p75-dependent and independent activity assays. Selected compounds 6, 9, 10, and 12 were also able to affect the exchange of the HIV-1 IN-IN subunit and the interaction between IN and LEDGF/p75. Differently from LEDGINs, small-molecule inhibitors were able to interact with the IN binding domain (IBD) of Lens-Epithelium-derived Growth Factor/p75 (LEDGF/p75) and HIV-1 IN, and none of these compounds was able to induce multimerization, sugges

SUBMITTER: Tocco G 

PROVIDER: S-EPMC12735844 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature