# Semi-Synthetic H2S Releasing Compounds with Antioxidant and Vasorelaxant Properties

## TL;DR

This paper introduces new compounds that release hydrogen sulfide and activate antioxidant pathways, potentially offering a new treatment for hypertension.

## Contribution

The study introduces hybrid compounds that combine H2S release with Nrf2 pathway activation for treating hypertension.

## Key findings

- Compound 8b effectively releases H2S and activates Nrf2-dependent antioxidant responses.
- Compound 8b reduces ROS production and cytotoxicity in injured cells and induces vasorelaxation.
- The compound's effects were observed in both human cells and isolated rat aortic rings.

## Abstract

Hypertension represents a severe cardiovascular pathology
linked
to the increase in reactive oxygen species that impair blood vessel
function. Herein, we report on the synthesis of hybrid compounds designed
to release H2S and incorporate natural or semisynthetic
scaffolds capable of activating the Nrf2 pathway. The molecular hybrids
enable a multitarget approach concurrently inducing vasorelaxation
upon H2S release and mitigating oxidative stress through
Nrf2-dependent antioxidant responses via the upregulation of cytoprotective
proteins, including HO-1. The itaconate derivative 8b displayed an optimal H2S release in both amperometric
and cellular assays. In human aortic smooth muscle cells, compound 8b counteracted ROS production and cytotoxicity in H2O2-injured cells and led to the activation of potassium
channels with consequent cell hyperpolarization and vasorelaxation,
which was also observed in isolated rat aortic rings. Overall, our
findings indicate that simultaneous Nrf2 activation and H2S release hold significant potential as a new therapeutic strategy
for the treatment of hypertension.