Synthesis and evaluation of analgesic, anti-inflammatory and antimicrobial activities of 6-acyl-3-piperazinomethyl-2-benzoxazolinones.

In this study, 16 new 6-difluorobenzoyl-3-piperazinomethyl-2-benzoxazolinones were synthesized by Mannich reaction. Their chemical structures were proven by IR, 1H-NMR and elemental analysis. The compounds were screened for their analgesic and anti-inflammatory activities. A modified Koster test, using acetylsalicylic acid (ASA, CAS 50-78-2) as the reference drug, was used to assess analgesic activity. The anti-inflammatory activity was evaluated by the carrageenan induced hind-paw oedema test. The analgesic activities of all compounds were higher than their anti-inflammatory activities and therefore the prominent analgesic actions of the compounds are thought to be due to a central effect. The microbiological effects of the compounds were evaluated in vitro against various pathogenic fungi and bacteria using the microdilution method. Most of the compounds were found to be inactive against bacteria and fungi. One of the compounds (31) possessed considerable analgesic activity as well as moderate antibacterial activity against S. aureus. Another compound (3m) showed analgesic and antifungal activities comparable to those of ASA and fluconazole (CAS 86386-73-4), respectively.

Inhibition of L-arginine transport by reactive oxygen species in rat anococcygeus muscle.

The effect of L-arginine on nitrergic transmission and its alteration with reactive oxygen species (ROS) were investigated. L-arginine potentiated the relaxation response induced by electrical field stimulation in rat anococygeus muscle. This effect was inhibited by L-lysine, a cationic amino acid using y+ L and y+ transport systems in a similar way with L-arginine. The neutral amino acid L-leucine, which uses only y+ L system as a transport mechanism, inhibited this potentiation at only low frequency stimulation. Electrolysis of the physiological solution did not change the responses to electrical field stimulation, but inhibited the potentiation elicited by L-arginine that was prevented in the presence of mannitol and N-acetyl-L-cysteine. In conclusion, L-arginine is transported via y+ system predominantly to potentiate the relaxation response to nitrergic nerve stimulation in rat anococcygeus muscle. ROS, primarily hydroxyl radicals inhibited L-arginine-induced potentiation probably by interacting with the y+ amino acid transport system.

Synthesis and anti-inflammatory activity of 1-acylthiosemicarbazides, 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazole-3-thiones.

Sixteen 1-(2-naphthyloxyacetyl)-4-substituted-3-thiosemicarbazide, 2-(2-naphthyloxymethyl)-5-substitutedamino-1,3,4-oxadiazole, 2-(2-naphthyloxymethyl)-5-substitutedamino-1,3,4-thiadiazole and 5-(2-naphthyloxymethyl)-4-substituted-1,2,4-triazole-3thione derivatives have been prepared and evaluated as orally active anti-inflammatory agents with reduced side-effects. The structures of the compounds were confirmed by IR and 1H NMR spectral data and microanalysis. The anti-inflammatory and ulcerogenic activities of the compounds were compared with naproxen, indomethacin and phenylbutazone. In carrageenan-induced foot pad edema assay, 2-(2-naphthyloxymethyl)-5-methylamino-1,3,4-oxadiazole, 5-(2-naphthyloxymethyl)-4-methyl-1,2,4-triazole-3-thione and 5-(2-naphthyloxymethyl)-4-ethyl-1,2,4-triazole-3-thione showed an interesting anti-inflammatory activity. In the air-pouch test, 1,3,4-oxadiazole and 1,2,4-triazole-3-thione derivatives reduced total number of leukocytes of the exudate that indicates excellent inhibition of prostaglandin production. Side effects of the compounds were examined on gastric mucosa, liver and stomach and none of the compounds showed significant side effects compared with reference nonsteroidal anti-inflammatory drugs (NSAIDs).