Uses
Hydrogen sulfide (H2S) is a naturally occurring gasotransmitter with vasodilator and inflammatory modulating activity. Non-steroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, diclofenac, and ibuprofen, are some of the most commonly used anti-inflammatory drugs available but exhibit significant side effects, particularly gastric damage, when used chronically. ATB-337 is a hybrid molecule of an H2S donor and the NSAID diclofenac. In rats, diclofenac at 10-50 μmol/kg caused significant gastrointestinal damage, whereas no damage was observed with ATB-337 treatment at the same dose. ATB-337 at 50 μmol/kg does not promote leukocyte adherence to vascular endothelium, an effect observed with diclofenac treatment alone. COX-1 and COX-2 were inhibited with similar efficacy by diclofenac and ABT-337. An increase in expression of the pro-inflammatory mediator TNF-α, as well as, the adhesion molecules ICAM-1 and LFA-1 were not observed in rats treated with 50 μmol/kg ABT-337, effects seen with equimolar doses of diclofenac. These results indicate that H2S-releasing derivatives of NSAIDs may prove to be more effective anti-inflammatory agents than traditional NSAIDs alone.[Cayman Chemical]
Biological Activity
atb-337 is a hybrid molecule of an h2s donor and the nsaid diclofenac [1].hydrogen sulfide (h2s) is a newly recognized signaling molecule with potent cytoprotective actions. hydrogen sulfide has been involved in mediating many physiological processes, such as the maintenance of gastrointestinal mucosal defense and repair. hydrogen sulfide also exerts many anti-inflammatory effects, including inhibition of leukocyte adherence to the vascular endothelium and leukocyte migration to sites of inflammation [2].oral administration of atb-337 did not produce any hemorrhagic erosions. oral administration of an equimolar dose of atb-337 produced > 90% less small intestinal damage and showed no significant effect on the hematocrit. in rats, administration of atb-337 (50 μmol/kg) showed no significant effect on leukocyte adherence. oral administration of atb-337 significantly increased plasma levels of h2s by > 40%. in a rat air pouch model, atb-337 (1 μmol/kg) suppressed cox-2 activity. in the rat, atb-337 inhibited thromboxane synthesis. atb-337 suppressed arachidonic acid–induced human platelet aggregation. pretreatment with atb-337 (10 μmol/kg) reduced paw swelling. atb-337 generated ～12nmol/min of h2s when it was incubated in buffer.
References
[1] wallace j l, caliendo g, santagada v, et al. gastrointestinal safety and anti-inflammatory effects of a hydrogen sulfide–releasing diclofenac derivative in the rat[j]. gastroenterology, 2007, 132(1): 261-271.
[2] wallace j l. physiological and pathophysiological roles of hydrogen sulfide in the gastrointestinal tract[j]. antioxidants & redox signaling, 2010, 12(9): 1125-1133.
