CHANGES IN HISTAMINE CONTENT FOLLOWING PHARMACOLOGICALLY-INDUCED MAST CELL DEGRANULATION IN THE RAT CONJUNCTIVA

Compound 48/80 was applied into one eye of male Wistar rats and a drop of vehicle into the contralateral eye. Another group of rats received sodium cromoglycate in both eyes every 6 h for a period of 48 h. One eye was challenged with compound 48/80 30 min after the end of treatment with sodium cromoglycate. The eyes were monitored clinically and the histamine content of the conjunctiva was determined fluorometrically. The basal histamine levels in rat conjunctival homogenates were quantified. Pharmacologically-induced mast cell degranulation by a single application of 0.1 g ml(-1)of compound 48/80 resulted in significant decreases of conjunctival histamine levels 1, 12 and 24 h after challenge. Sodium cromoglycate prevented the effect of compound 48/80 when administered into the eye prior to the challenge with the non-immunogenic histamine releaser. Upon termination of the application, the membrane stabilizer was unable to reverse the reduced histamine levels in the conjunctival homogenates.     

Medicinal Chemistry: Synthesis and Pharmacochemical Investigation of Some Novel 1, 2, 4-4H-triazoles with Potential Antiviral Activity

We report the synthesis of some mercaptotriazole derivatives in an effort to discover underlying structural requirements for antiviral activity. A preliminary antiviral study was performed and the contribution of the compounds to free radical processes was investigated. Because lipophilicity influences both biological activity and antioxidant potential we calculated lipophilicity and attempted to correlate this with antioxidant activity. Treatment of the N-(aryl)piperazineacetohydrazides (compounds 1 ) with 2, 4-dichloro-phenylisothiocyanate gave the N-(aryl)piperazinethiosemicarbazides (compounds 2 ) in good yield. Cyclization of these compounds after treatment with NaOH solution provided the corresponding 5-(4-aryl-1-piperazinylmethyl)-4-(2, 4-dichlorophenyl)-4H-1, 2, 4-triazole-3-thiols (compounds 3 ) in good yield. Reaction of compounds 3 with 2, 4-dichloro-or 4-fluorobenzyl chloride in acetone in the presence of potassium carbonate gave the target compounds (compounds 4 ) in about 70% yield. The antioxidant effect of the compounds on non-enzymatic lipid peroxidation of rat hepatic microsomal membranes was studied. Most of the examined compounds were active at concentration of 0.1 mM and most were found to prevent dimethylsulphoxide oxidation moderately (20–50%) at a concentration tenfold less than that of dimethylsulphoxide. The interaction of the synthesized compounds with 1, 1-diphenyl-2-picrylhydrazyl stable free radical was also studied. Correlation was found between the two expressions of calculated lipophilicity, antioxidant activity and the lipophilicity of the synthesized compounds, and a correlation was derived between antioxidant activity and logP, which expresses the compounds' hydrogenbonding capacity.