Design, synthesis, and biologic evaluation of novel galloyl derivatives as HIV-1 RNase H inhibitors.

ABSTRACT: Human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated ribonuclease H (RNase H) remains as the only enzyme encoded within the viral genome not targeted by current antiviral drugs. In this work, we report the design, synthesis, and biologic evaluation of a novel series of galloyl derivatives with HIV-1 RNase H inhibitory activity. Most of them showed IC₅₀ s at sub- to low-micromolar concentrations in enzymatic assays. The most potent compound was II-25 that showed an IC₅₀ of 0.72 ± 0.07 μM in RNase H inhibition assays carried out with the HIV-1_BH10 RT. II-25 was 2.8 times more potent than β-thujaplicinol in these assays. Interestingly, II-25 and other galloyl derivatives were also found to inhibit the HIV IN strand transfer activ

SUBMITTER: Gao P 

PROVIDER: S-EPMC7441570 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature