Design,synthesis and cholinesterase inhibitory properties of new oxazole benzylamine derivatives

Abstract

The enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are primary targets in attenuating the symptoms of neurodegenerative diseases. Their inhibition results in elevated concentrations of the neurotransmitter acetylcholine which supports communication among nerve cells. It was previously shown for trans-4/5-arylethenyloxazole compounds to have moderate AChE and BChE inhibitory properties. A preliminary docking study showed that elongating oxazole molecules and adding a new NH group could make them more prone to bind to the active site of both enzymes. Therefore, new trans-amino-4-/5-arylethenyl-oxazoles were designed and synthesised by the Buchwald-Hartwig amination of a previously synthesised trans-chloro-arylethenyloxazole derivative. Additionally, naphthoxazole benzylamine photoproducts were obtained by efficient photochemical electrocyclization reaction. Novel compounds were tested as inhibitors of both AChE and BChE. All of the compounds exhibited binding preference for BChE over AChE, especially for trans-amino-4-/5-arylethenyl-oxazole derivatives which inhibited BChE potently (IC₅₀ in µM range) and AChE poorly (IC₅₀?100?µM). Therefore, due to the selectivity of all of the tested compounds for binding to BChE, these compounds could be applied for further development of cholinesterase selective inhibitors.

• HIGHLIGHTS

• Series of oxazole benzylamines were designed and synthesised

• The tested compounds showed binding selectivity for BChE

• Naphthoxazoles were more potent AChE inhibitors

     

Macrohistone Variants Preserve Cell Identity by Preventing the Gain of H3K4me2 during Reprogramming to Pluripotency

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Highlights? Macrohistone variants are regulated during reprogramming and differentiation ? The levels of macrohistone variants modulate the efficiency of reprogramming ? MacroH2A.1 occupies pluripotency and differentiation genes in keratinocytes ? MacroH2A.1 occupancy prevents the gain of H3K4me2 during reprogramming     

Causes and consequences of DNA repair activity modulation during stationary phase in Escherichia coli

Escherichia coli responds to nutrient exhaustion by entering a state commonly referred to as the stationary phase. Cells entering the stationary phase redirect metabolic circuits to scavenge any available nutrients and become resistant to different stresses. However, many DNA repair pathways are downregulated in stationary-phase cells, which results in increased mutation rates. DNA repair activity generally depends on consumption of energy and often requires de novo proteins synthesis. Consequently, unless stringently regulated during stationary phase, DNA repair activities may lead to an irreversible depletion of energy sources and, therefore to cell death. Most stationary phase morphological and physiological modifications are regulated by an alternative RNA polymerase sigma factor RpoS. However, nutrient availability, and the frequency and nature of stresses, are different in distinct environmental niches, which impose conflicting choices that result in selection of the loss or of the modification of RpoS function. Consequently, DNA repair activity, which is partially controlled by RpoS, is differently modulated in different environments. This results in the variable mutation rates among different E. coli ecotypes. Hence, the polymorphism of mutation rates in natural E. coli populations can be viewed as a byproduct of the selection for improved fitness.     

Importance of correct therapeutic procedure selection in voice recovery

Psychological and physical patient state as well as the influence of other social factor is of great influence voice rehabilitation. A team of experts in the field of voice and its function are involved in voice therapy. Our research was focused on the successfulness of voice recovery depending on the patient vocal disorder approach. We made a comparison of two methods: RVT and Accent method. We attempted to evaluate clinically relevant voice disorders in relation to certain vocal methods, we propose that a lot can be learned about voice trough therapeutic procedures, which can also be used to enhance the practical application of vocal methods and raise the level of success in dealing with people that suffer from voice pathology.     

The case report of treatment strategy for Anorexia nervosa with psychotic elements in adolescent

Eating disorders in early childhood are the same frequency in boys and girls. During adolescence eating disorders are ten (10) times more frequent in girls than in boys. Worrying is the fact that eating disorders are the third chronic illness among adolescents after obesity and asthma. Depicting this adolescent we tried to show difficulty of treatment of this disorder, where in the beginning is important to stabilize body weight and prevent somatic damages such as: heart damage, amenorrhoea, changes in EKG (electrocardiogram) and electrolyte dysbalance that could endanger the life of patient. Simultaneously it is important to recognize and treat comorbid psychological disturbances such as in this case: depression, delusions with occasional psychotic reactions combined with unrealistic thinking about the layout of her own body. There is still no cure for the treatment of eating disorders which are in growing number of reports among male adolescents.     

Differentiation between Candida species isolated from diabetic foot by fatty acid methyl ester analysis using gas chromatography

Gas chromatography (GC) was used to differentiate 100 isolates of Candida species (Candida parapsilosis, Candida albicans, Candida tropicalis, Candida famata and Candida glabrata) from 22 of 509 diabetic patients in whom the same species had been isolated from ulcer and interdigital spaces of the same and/or the other foot. All clinical isolates were identified by quantitative differences in the composition of six cell fatty acids (CFA). The values of the coefficients of variability (CV) of CFA show that the isolates from foot ulcers and interdigital spaces of the same diabetic patient probably belong to different chemotypes of the same Candida species.     

The treatment of autistic children with risperidone

Autism is a pervasive developmental disorder characterised by impairment in social interaction and communication, with unusual behavior. In some cases the pharmacotherapy is prescribed and the most studied antipshychotic drugs include haloperidol and risperidone. In this paper we displayed the treatment of two cases of autism in boy and girl with risperidone. With the use of risperidone in girl, we have achieved reduction of psychomotor symptoms and reduction of hetero-aggressive and self-destructive behavior, and in boy we have also achieved reduction of psychomotoric symptoms, with improvement in contact with his surrounding, he had less learning problems and he has felt familiar not only with his mother, but with other persons. Research on the use of risperidone in the treatment of autistic disorders among children in Croatia are rare, given the limited use of risperidone in children younger than 15years, the question arises about the need to expand the scope of application of risperidone in younger age groups.