Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide 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 H 2 S and incorporate natural or semisynthetic scaffolds capable of activating the Nrf2 pathway. The molecular hybrids enable a multitarget approach concurrently inducing vasorelaxation upon H 2 S 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 H 2 S release in both amperometric and cellular assays. In human aortic smooth muscle cells, compound 8b counteracted ROS production and cytotoxicity in H 2 O 2 -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 H 2 S release hold significant potential as a new therapeutic strategy for the treatment of hypertension.
Source: ACS Medicinal Chemistry Letters
Authors: Valentina Citi, Antonino N. Fallica, Loredana Salerno, Nicola F. Virzì, Valeria Ciaffaglione, Sebastiano Intagliata, Sara Veneziano, Giada Benedetti, Jacopo Spezzini, Alma Martelli, Vincenzo Calderone, Valeria Pittalà
Institutions: University of Pisa, University of Catania
Language: English
Topic: Sulfur Compounds in Biology
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W4417133245