Benzo Different Anti-inflammatory Effects Of Selenium Trazodone Sulfonamide Derivatives

Arachidonic acid(AA) presents in the cell membrane in its esterified form. Trauma, infection and inflammation are able to cause a receptor-mediated influx of calcium ion, and cytosolic phospholipase A₂ translocation to the cell membrane .The enzyme then catalyzes the hydrolysis of the ester of AA to free from of AA . Arachidonic acid is metabolized through two routes. The first way is to convert AA into leukotriene A₄ catalyzed by 5-lipoxygenase. The formation of LTA₄ is the proceeding step in the synthesis of LTB₄ on the one hand and of the sulfidopeptide or cysteinyl leukotrienes(LTC₄, LTD₄ and LTE₄) on the other. LTB₄ is probably the most potent neutrophil chemotactic agent produced by the arachidonic acid cascade, it also plays a pivotal role in the induction of neutrophil-endothelial cell adherence and neutrophil degranulation and lysosomal enzyme release. The sulfidopeptide leukotrienes can play a multifaceted role the inflammatory process, inducing vasoconstriction, increasing vasopemeability, enhancing mucous secretion, and acting as immunomodulatory agent.Arachidonic acid also can be converted into prostaglandins, prostacyclin and thromboxanes by cyclooxygenase. A significant clarification arose with the discovery of a second distinct isoform of cyclooxygenase: COX-1 and COX-2. COX-1 is a constitutive enzyme responsible for the production of prostanoids necessary for platelet aggregation and protection of the endothelium, the gastric mucosa and the kidney; COX-2, an inducible enzyme is newly synthesised at sites of tissue damage and produces prostaglandins that manifest pathological effects. It became clear that different NSAIDs had greater or lesser effects on COX-1 when used in doses sufficient to inhibit COX-2 (the therapeutic dose) , explaining the variations in side-effects.In this paper , a series of ebselen derivatives were studied to investigate their effects on LTB₄ biosynthesis and the preliminary structure-activity relationship(SAR) of these compounds were described. It was found that sulfonamide analogues of ebselen and N-aryl substituted derivatives of ebselen have significant inhibitory effects on LTB4 biosynthesis with IC₅₀ of 10^-5mol · L(-1)to10^-6mol · L^-1. According to SAR , the presence of an acidic hydrogen atom on sulfonamido group seems to be critical factor for the activity. In the absence of the hydrogen or loss...