Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H Inhibitors

Targeting ribonuclease H (RNase H) has emerged as a highly promising strategy for treating HIV-1. In this study, a series of novel 3-hydrazonoindolin-2-one derivatives were designed and synthesized as potential inhibitors of HIV-1 RNase H. Notably, several of these derivatives displayed micromolar inhibitory activity. Among the compounds examined, the hit compound demonstrated potent inhibition of HIV-1 RNase H, boasting a Ki value of 2.31 μM. Additionally, the most potent compound of this general structure exhibited remarkable inhibitory activity, with Ki values of 0.55 μM. Through docking studies, the key interactions of this ligand within the active site of RNase H were uncovered. This novel chemical structure can be regarded as a prospective scaffold for the future development of RNase H inhibitors.

Authors

Institutions

Publication Details

Journal
Molecules
Published
2025-04-22
DOI
https://doi.org/10.3390/molecules30091868
Primary Topic
HIV/AIDS drug development and treatment
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H Inhibitors

Christophe Pannecouque, Robert Wang, Fen‐Er Chen, Enzo Tramontano et al.
Molecules
HIV/AIDS drug development and treatment
article

Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H Inhibitors

Christophe Pannecouque, Robert Wang, Fen‐Er Chen, Enzo Tramontano, Erik De Clercq, Angela Corona, Laura Dettori, Shuai Wang, Yang Bu, Yiying Zhang, Ge Meng
article en

Abstract

Targeting ribonuclease H (RNase H) has emerged as a highly promising strategy for treating HIV-1. In this study, a series of novel 3-hydrazonoindolin-2-one derivatives were designed and synthesized as potential inhibitors of HIV-1 RNase H. Notably, several of these derivatives displayed micromolar inhibitory activity. Among the compounds examined, the hit compound demonstrated potent inhibition of HIV-1 RNase H, boasting a Ki value of 2.31 μM. Additionally, the most potent compound of this general structure exhibited remarkable inhibitory activity, with Ki values of 0.55 μM. Through docking studies, the key interactions of this ligand within the active site of RNase H were uncovered. This novel chemical structure can be regarded as a prospective scaffold for the future development of RNase H inhibitors.

MoleculesVol. 30(9)
University of Cagliari (IT), Yunnan University (CN), Rega Institute for Medical Research (BE), Fudan University (CN), University of Pavia (IT), Zhengzhou University (CN), Puer University (CN), KU Leuven (BE)
National Natural Science Foundation of China
Good health and well-being
Openalex Percentile: Top 89%
HIV/AIDS drug development and treatment
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.

Design, Synthesis and Biological Evaluation of 3-Hydrazonoindolin-2-one Derivatives as Novel HIV-1 RNase H Inhibitors — Christophe Pannecouque, Robert Wang, et al. · Molecules (2025) | TGRS Research Map | TGRS