Activity evaluation of multifunctional HS donors for anti-inflammatory, cardioprotective, and hepatoprotective applications.

INTRODUCTION

As an important gas signaling molecule, hydrogen sulfide (HS) exhibits therapeutic potential in inflammatory and oxidative stress-related diseases. This study developed and evaluated novel HS donor derivatives based on the phenylphosphonothioic dichloride scaffold.

METHODS

Derivatives were synthesized based on the phenylphosphonothioic dichloride scaffold. Compound was selected for its high HS release capacity and favorable safety profile. Its anti-inflammatory activity was evaluated by measuring inhibition of TNF-α, TNF-β, and nitrite. Hepatoprotective effects were assessed in an HO-induced injury model using oxidative stress markers (MDA, SOD, GSH) and HSC activation. Cardioprotective effects were examined in an LPS-induced model by analyzing mitochondrial membrane potential, cardiac markers (LDH, CK-MB), and oxidative balance.

RESULTS

Compound showed the highest H2S release capacity and inhibited TNF-α (86%), TNF-β (82%), and nitrite (67%). In the hepatocyte model, it reduced MDA (79%), enhanced SOD (49%) and GSH (76%), and suppressed HSC activation (55%). In the myocardial model, attenuated mitochondrial membrane potential dissipation, decreased LDH (34%) and CK-MB (24%), and restored GSH activity (73%) while reducing MDA (48%).

DISCUSSION

The phosphorus-sulfur scaffold-based HS donor demonstrates synergistic anti-inflammatory, antioxidant, and organ-protective effects, highlighting its promise as a drug candidate for treating inflammation- and oxidative stress-related disorders.