Synthesis of New Ester Derivatives of Salicylic Acid and Evaluation of Their COX Inhibitory Potential

Salicylic acid is an NSAID with serious side effects on the GIS. The side effects of salicylic acid on the GIS are slightly reduced by acetylating salicylic acid. 12 new ester analogs of salicylic acid were synthesized with high yields in this study. The chemical structures of the synthesized compounds were characterized by ¹H-NMR, ¹³C-NMR, and HRMS spectra. The inhibitory potential of the compounds was evaluated on COXs by in vitro and in silico studies. The COX2 inhibitory activity of the most potent inhibitor MEST1 (IC₅₀: 0.048 μM) was found to be much higher than the COX2 inhibitory activity of aspirin (IC₅₀: 2.60 μM). In docking studies, the strongest inhibitor among the compounds synthesized was predicted to be MEST1, with the lowest binding energy. Docking studies revealed that MEST1 extends from the hydrophobic channel to the top of the cyclooxygenase active site, forming various interactions with residues in the binding pocket.     

A current approach to the control of filamentous fungal growth in media: microparticle enhanced cultivation technique

Various strategies have been carried out to date in order to overcome the problem of the adverse effects of bulk fungal growth in bioreactors. Nevertheless, previous conventional methods such as modifying the cultivation temperature or pH resulted in limited biomass production and consequently lower yields. In recent years microparticle enhanced cultivation (MPEC) techniques are one of the most remarkable and novel methods employed for submerged fungal production to overcome bulk microbial growth. In addition to low cost advantages, MPEC also provides benefits such as not interfering with fungal metabolism, enhancing final product concentration and improving homogeneity in the fermentation broth. In this review, a comparison of conventional and novel methods to control fungal morphology has been discussed. Additionally, the application of microparticles in fungal fermentations, their benefits to the process in terms of fungal morphology, biomass accumulation, substrate consumption, and product formation also effect mechanisms of microparticle function are discussed in detail.     

An Epigenetic Priming Mechanism Mediated by Nutrient Sensing Regulates Transcriptional Output during C. elegans Development

1. Download : Download high-res image (133KB)
2. Download : Download full-size image

     

Iloprost preserves kidney function against anoxia

Tissue protective activity of iloprost against anoxia was studied in the isolated perfused rabbit kidney. Addition of iloprost to the perfusion medium at concentrations between 10(-9)-10(-7) M attenuated the release of noradrenaline due to periarterial stimulation and decreased urine outflow. Iloprost also caused a concentration-dependent decrease in perfusion pressure. The potentiation by angiotensin II of the vasoconstriction due to periarterial stimulation and increase in urine volume were also decreased by further addition of iloprost into the medium. Iloprost at concentrations below 10(-7) M did not alter the vasoconstrictor effect of exogenously applied noradrenaline. UK 38 485, a powerful thromboxane A2 synthetase inhibitor, significantly suppressed the vascular but greatly potentiated the diuretic effects of angiotensin II. In kidneys exposed to anoxia for 24 hours in Krebs medium, the vascular and diuretic effects of angiotensin II and the release of noradrenaline due to periarterial stimulation were significantly diminished. In addition, interation between UK 38 485 and angiotensin II in both perfusion pressure and urine volume was also reduced after anoxia for 24 hours. On the other hand, no significant loss was observed in all investigated parameters measured in this study, in kidneys exposed to anoxia for 48 hours in the presence of iloprost. From these results it was concluded that iloprost preserves kidneys functionally against anoxia and possible mechanisms of this effect are discussed.