ORIGINAL RESEARCH article
Front. Chem.
Sec. Medicinal and Pharmaceutical Chemistry
Volume 13 - 2025 | doi: 10.3389/fchem.2025.1643663
Activity Evaluation of Multifunctional H₂S Donors for Anti-Inflammatory, Cardioprotective, and Hepatoprotective Applications
Provisionally accepted
- The Second Hospital of Qinhuangdao, Qinhuangdao, China
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This study constructed previously reported H₂S donor derivatives based on the phenylphosphonothioic dichloride scaffold. Activity screening identified compound 3b-1 with the highest H₂S release capacity and favorable safety profile. Evaluation of anti-inflammatory activity demonstrated 3b-1's significant inhibition of key inflammatory mediators: TNF-α (86%), TNF-β (82%), and nitrite (67%). In an H₂O₂-induced hepatocyte injury model, 3b-1 (50 μg/mL) modulated oxidative stress balance by reducing the lipid peroxidation product MDA (79%), enhancing antioxidant enzyme activities of SOD (49%) and GSH (76%), and suppressing HSC activation (55%), effectively reversing liver damage and exhibiting antifibrotic potential. In an LPS-induced myocardial injury model, 3b-1 (50 μg/mL) attenuated mitochondrial membrane potential dissipation, decreased cardiac injury markers LDH (34%) and CK-MB (24%), and restored GSH activity (73%) while reducing MDA levels (48%), confirming cardioprotective effects. As a phosphorus-sulfur scaffold-based H₂S donor, 3b-1 achieves tripartite synergistic effects (anti-inflammatory, antioxidant, and organ-protective), positioning it as a highly promising drug candidate molecule for development.
Keywords: Hydrogen Sulfide, Cardioprotective, Hepatoprotective, anti-inflammatory, Phenylthiophosphonic dichloride
Received: 09 Jun 2025; Accepted: 15 Aug 2025.
Copyright: © 2025 Wang, Meng and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Donghe Wang, The Second Hospital of Qinhuangdao, Qinhuangdao, China
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