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

Journal Article (Journal Article)

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-1BH 10 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 activity in vitro. Structure-activity relationships (SAR) studies and molecular modeling analysis predict key interactions with RT residues His539 and Arg557, while providing helpful insight for further optimization of selected compounds.

Full Text

Duke Authors

Cited Authors

  • Gao, P; Wang, X; Sun, L; Cheng, X; Poongavanam, V; Kongsted, J; Álvarez, M; Luczkowiak, J; Pannecouque, C; De Clercq, E; Lee, K-H; Chen, C-H; Liu, H; Menéndez-Arias, L; Liu, X; Zhan, P

Published Date

  • April 2019

Published In

Volume / Issue

  • 93 / 4

Start / End Page

  • 582 - 589

PubMed ID

  • 30560566

Pubmed Central ID

  • PMC7441570

Electronic International Standard Serial Number (EISSN)

  • 1747-0285

Digital Object Identifier (DOI)

  • 10.1111/cbdd.13455


  • eng

Conference Location

  • England