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

## TL;DR

This paper reports the design and testing of new compounds that inhibit an HIV enzyme, showing promising results for future HIV treatments.

## Contribution

The study introduces a novel chemical scaffold with potent HIV-1 RNase H inhibitory activity.

## Key findings

- Several 3-hydrazonoindolin-2-one derivatives showed micromolar inhibitory activity against HIV-1 RNase H.
- The most potent compound had a Ki value of 0.55 μM, indicating strong inhibition.
- Docking studies revealed key interactions of the compound within the RNase H active site.

## 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.