A series of benzo[h][1,6]naphthyridine and azepino[3,2-c]quinoline derivatives were prepared and evaluated to determine the necessary requirements for high affinity on the 5-HT(4) receptors and high selectivity versus other receptors. The compounds were synthesized by substituting the chlorine atom of benzonaphthyridines and azepinoquinolines with various N-alkyl-4-piperidinylmethanolates. They were evaluated in binding assays with [(3)H]GR 113808 as the 5-HT(4) receptor radioligand. The affinity values (K(i) or inhibition percentages) depended upon the substituent on the aromatic ring on one hand and the substituent on the lateral piperidine chain on the other hand. A chlorine atom produced a marked drop in activity while a N-propyl or N-butyl group gave compounds with nanomolar affinities (1 < K(i) < 10 nM). Among the most potent ligands (3a, 4a, 5a), 4a was selected on the basis of its high affinity and selectivity for pharmacological screening and was evaluated in vivo in specific tests. This compound reveals itself as an antagonist/low partial agonist in the COS-7 cells stably expressing the 5-HT(4(a)) receptor. Derivative 4a also showed in vivo potent analgesic activity in the writhing test at very low doses.

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Heat shock proteins (HSP70) play a significant role in adaptation to temperature and have been proposed as an indicator of cellular stress. Since the water temperature in Kuwait's marine area varies from 13 to 35 degrees C from winter to summer, HSP70 could be a valuable tool in aquaculture in Kuwait. HSP70 levels were quantified by Western blotting in liver, muscle and gill tissues of two varieties of native fish species captured during the winter and summer months from both inside and outside the highly stressed Kuwait Bay area. The HSP70 levels did not differ statistically between fish captured from the two sampling areas. The most common response in both species was higher median levels of HSP70 in winter months. This inverse relation between HSP70 levels in the fish and the water temperature may be due to either genetic adaptation in the fish to the hot climatic conditions of the region or other stressors, such as changes in pollutant levels in the surrounding water.

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The health of a marine ecosystem can effectively be monitored by studying the levels of biomarkers in a representative species. A change in background level of a biomarker indicates exposure to a specific type of pollutants. It also identifies bioavailability and the organism response to the causative agent among the compounds present in the surrounding water body. Yellowfin seabream (Acanthopagrus latus), a local variety of fish, was examined for parent PAHs in the liver, its metabolites in bile by the GC-MS method as exposure biomarkers and cytochrome P4501A1 by assay of ethoxyresorufin-o-deethylase (EROD) in the liver as an effect biomarker. A comparison was made between fish collected in 2015 with the fish collected in 2005-2006 and stored at - 80 °C in the fish bank. The objective was to examine the extent of changes in the environmental quality of the Kuwait marine area and the status of fish health concerning oil-related pollutants since Arabian Gulf is surrounded by oil-producing countries. Interestingly, insignificant differences between the liver PAH content and EROD activity were observed in fish over the sampling periods. The fish efficiently metabolized PAHs and excreted hydroxy-metabolites in bile. The study suggested that environmental quality of the Kuwait marine area was not deteriorated to any serious extent in the last decade and biomarkers can be used effectively in assessing the thrust of sub-optimal levels of various contaminants present in the marine area on the resident biota.

Using solid phase synthesis techniques, we have rapidly obtained a series of eight aryl sulphonamides derived from putrescine. These conjugates with various aryl groups were evaluated for their affinity towards 5-HT6 receptors in man. This evaluation revealed the interest of two compounds which present the same activity level, in the submicromolar range, as two reference derivatives. The most potent will be considered as a new lead for further investigations.

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A series of N-omega-aminoalkyl- or N-omega-amidinoalkyl-2,4,6-triisopropyl benzenesulfonamides has been synthesized and their respective affinity indices on 5-HT6 receptor determined. This evaluation clearly showed that the compounds possessing an arylpiperazine moiety or an amidine function exhibited good affinity for the model.