Chromatographic separation and spectroscopic characterization of the e/z isomers of acrivastine

A reverse phase high performance liquid chromatography (HPLC) method has been developed for the separation of two geometric isomers of Acrivastine using crude reaction mixture. The resolution between two isomers was found more than 2.9. The geometric isomers have been isolated by preparative HPLC and characterized by spectroscopic techniques, such as NMR, infrared, and MS. The developed method has been validated for the determination of Z‐isomer in Acrivastine. The limit of detection and limit of quantification of the Z‐isomer were 0.05 and 0.2 μg/ml, respectively. The developed method is precise, linear, accurate, rugged and robust for its intended use. Chirality, 2011. © 2011 Wiley‐Liss, Inc.     

Antiatherosclerotic activity of ibuprofen, a non-selective COX inhibitor--an animal study

Atherosclerosis being considered as an inflammatory disorder, the present study was undertaken to investigate the effectiveness of anti-inflammatory drugs (ibuprofen, aspirin, and celecoxib) in hypercholesterolemia. Ibuprofen is a cyclooxygenase (COX-1 and COX-2) inhibitor known to reduce the production of prostaglandins that play prominent role in inflammation. Beside the anti-inflammatory effects that make ibuprofen interesting for the treatment of condition associated with hypercholesterolemic atherosclerosis. Various other properties of ibuprofen were investigated, ibuprofen showed better reduction in total cholesterol, triglycerides, very low density lipo-protein, low density lipo-protein and atherogenic index than aspirin and celecoxib in hypercholesterolemic animals. These properties of ibuprofen may be due to inhibition of acetyl-CoA carboxylase initiating the synthesis of fatty acids. Ibuprofen significantly elevated antioxidant (super oxide dismutase; catalase) levels and reduced lipid peroxidation. Ibuprofen inhibits COX enzymes and thereby inhibits generation of free radicals during prostaglandins synthesis, which may be responsible for reduction in lipid peroxidation, super oxide dismutase levels and for high catalase levels. Interestingly, ibuprofen decreased total leukocyte count, monocyte count, erythrocyte sedimentation rate and C-reactive protein levels. From the results of present study, it can be concluded that ibuprofen (non-selective COX inhibitor) showed promising antihyperlipidemic, antiatherosclerotic, antioxidant, antiinflammatory and non-ulcerogenic activity in atherosclerotic animals as compared to aspirin (preferential COX-1 inhibitor) and celecoxib (selective COX-2 inhibitors, suggesting the inducible role of COX in atherosclerosis.     

Discrete Cyclic di-GMP-Dependent Control of Bacterial Predation versus Axenic Growth in Bdellovibrio bacteriovorus

Bdellovibrio bacteriovorus is a Delta-proteobacterium that oscillates between free-living growth and predation on Gram-negative bacteria including important pathogens of man, animals and plants. After entering the prey periplasm, killing the prey and replicating inside the prey bdelloplast, several motile B. bacteriovorus progeny cells emerge. The B. bacteriovorus HD100 genome encodes numerous proteins predicted to be involved in signalling via the secondary messenger cyclic di-GMP (c-di-GMP), which is known to affect bacterial lifestyle choices. We investigated the role of c-di-GMP signalling in B. bacteriovorus, focussing on the five GGDEF domain proteins that are predicted to function as diguanylyl cyclases initiating c-di-GMP signalling cascades. Inactivation of individual GGDEF domain genes resulted in remarkably distinct phenotypes. Deletion of dgcB (Bd0742) resulted in a predation impaired, obligately axenic mutant, while deletion of dgcC (Bd1434) resulted in the opposite, obligately predatory mutant. Deletion of dgcA (Bd0367) abolished gliding motility, producing bacteria capable of predatory invasion but unable to leave the exhausted prey. Complementation was achieved with wild type dgc genes, but not with GGAAF versions. Deletion of cdgA (Bd3125) substantially slowed predation; this was restored by wild type complementation. Deletion of dgcD (Bd3766) had no observable phenotype. In vitro assays showed that DgcA, DgcB, and DgcC were diguanylyl cyclases. CdgA lacks enzymatic activity but functions as a c-di-GMP receptor apparently in the DgcB pathway. Activity of DgcD was not detected. Deletion of DgcA strongly decreased the extractable c-di-GMP content of axenic Bdellovibrio cells. We show that c-di-GMP signalling pathways are essential for both the free-living and predatory lifestyles of B. bacteriovorus and that obligately predatory dgcC- can be made lacking a propensity to survive without predation of bacterial pathogens and thus possibly useful in anti-pathogen applications. In contrast to many studies in other bacteria, Bdellovibrio shows specificity and lack of overlap in c-di-GMP signalling pathways.     

Synthesis,Computational Insights,and Anticancer Activity of Novel Indole–Schiff Base Derivatives

Russian Journal of Bioorganic Chemistry - Synthetic and naturally available compounds with indole moiety are known to show significant biological activity. This paper describes computational...