Design, Synthesis and Bioassays of 3-substituted-3-hydroxyoxindoles for cholinesterase inhibition

Based on the positive bioassay results of the known oxindole hit compound rac-1-benzyl-3-hydroxy-3-phenylindolin-2-one which showed significant inhibition of butyrylcholinesterase (BuChE) (IC50=7.41 μM), a library of 31 analogues of 3-substituted-3-hydroxyoxindoles was synthesized and screened for both acetylcholinesterase (AChE) and BuChE activity. Our bioassays revealed that some of the new compounds exhibited moderate inhibition of eel AChE (EeAChE) and very good inhibition of equine serum BuChE (EqBuChE) with a best IC50 of 1.02 μM. On the basis of these results, the lead compound 1-((1-benzylpiperidin-4-yl)methyl)-3-hydroxy-3-phenylindolin-2-one was designed, which was shown to interact well with the enzymes active sites by molecular docking, was synthesized and upon bioassay gave an IC50 of 6.61 μM for BuChE. Interestingly, when we separated rac-benzyl-3-hydroxy-3-phenylindolin-2-one into the individual enantiomers (R)- and (S)-benzyl-3-hydroxy-3-phenylindolin-2-one it was the latter enantiomer that gave the best IC50 of 6.19 μM for BuChE.

Integrating life design counseling and psychotherapy: Possibilities and practices.

The debate on the relation between career counseling and psychotherapy revealed the close relation between psychosocial and career issues. The connection between these two approaches paves the way for the integration of career counseling into psychotherapy. One of the key challenges of integrating career counseling into psychotherapy is to avoid discontinuities and inconsistencies in the psychotherapeutic intervention. The aim of this article is, therefore, to present the Systematic Treatment Selection perspective as a framework for an effective integration of psychotherapy and career counseling. Then, Life Design Counseling is described, highlighting its possibilities to fit the psychotherapeutic approach. Finally, an illustrative case is presented and discussed.

Integrating Life-Design Counseling and Psychotherapy: Possibilities and Practices

The relationship between career counseling and psychotherapy is not a new subject. The debate allows the affirmation of career counseling as a dimension of personal counseling and recognizes the close relationship between psychosocial and career issues (Blustein & Spengler, 1995). The connection between these two approaches paves the way for the integration of career counseling with psychotherapy. Indeed, the inseparability of mental health and career issues frequently leads psychotherapists to help their clients to deal with work satisfaction, underemployment or unemployment through psychotherapy. Moreover, when working with specific populations (e.g., people with intellectual disabilities and people with addiction or mental health problems), psychotherapy calls for occupational integration to consolidate and enhance therapeutic gains (Blustein, 1987; Jordan & Kahnweiler, 1995; Leff & Warner, 2006).

Heterogeneous Catalysts: Design, Applications and Research Insights

The cyclization of pseudoionone yields a mixture of alpha-ionone, beta-ionone and gamma-ionone. By careful control of reagent and reaction conditions, either the alpha- and beta- isomer can be favoured. The alpha-ionone has violet odour and is widely used in perfumery and flavours. beta-Ionone is the main precursor of Vitamin A and beta-carotene. Traditionally, strong homogeneous catalysts, like sulphuric acid and phosphoric acid have been used. These problems can be overcome by the use of solid acid catalysts. This work reports the cyclization of pseudoionone over USY zeolites, at 80ºC. USY It is observed that the initial activity increases with the Si/Al ratio of zeolite until a maximum, which is obtained with USY3. With higher Si/Al ratio, a decrease in the catalytic activity is observed. Selectivity to ionone isomers is around 42 %, at 75% of pseudoionone conversion, after 24 h of reaction. USY3 zeolite was reused four times with the same catalyst sample in the same condicions. It was observed a stabilization of the catalytic activity, after the second use.

Creative Practices Around the Production of Cork

Cork, as a natural product provided by the bark of the cork oak tree, is an important staple of the Portuguese economy and important to Portuguese culture. It is a sustainable product with a positive ecological footprint, from harvesting to industrial production, with the advantage of creating a local economic model through regional labour activity and distribution. Within the balance between nature-human-economy to create a sustainable system, cork production in Portugal represents a human and social dimension. By focusing on that dimension and by creating an awareness of the cultural and social impact of the activity and by re-appraising the meaning of the material within the culture, the study reframes a consideration of the actual place of labour and production. The human, geophysical, historical, social, economic, ecological and cultural aspects of the place are observed as regards their relation to work or labour in that physical space. A pilot study is being developed in the village of Azaruja in the district of Évora, Portugal. In this small locality, cork is very important in terms of the relationships between the physical subsistence of their residents and the local natural resources, because it structures the place in its cultural, social and economical dimensions. This paper outlines the theoretical foundations, the process and the outcomes of the participatory ecodesign project titled Creative Practices Around the Production of Cork which was initiated by a Portuguese artist/design researcher and developed further through the collaboration with the other two authors, one a Portuguese visual artist/researcher and the other a Turkish fashion designer/theorist. The investigation focuses on questions that expand the notion of place for artists and designers, filtered through the lenses of manual labourers in order to understand their physical, social, cultural and economic relationship with the environment. To create the process of interaction with the place and the people, a creative collaborative dynamic is developed between the authors with their range of artistic sensibilities and the local population. To adopt a holistic notion of sustainability and cultural identity a process of investigation is designated to: (1) analyse, test and interpret - through the dissemination of life stories, visual representation of the place and the creation of cork objects - the importance of culture related to the labour activity of a local natural resource that determines and structures the region; (2) to give public recognition to those involved, taking into account their sense of belonging to the place and in order to show the value of their sustainable labour activities related to local natural resources; (3) to contribute to the knowledge of the place and to its dynamism through an aesthetic approach to labour activities. With reference to fields of knowledge such as anthropology, the social arts and sustainable design, a practice-based research is conducted with collaborative and participatory design methods to create an open model of interaction which involves local people in the realization of the project. Outcomes of this research will be presented in the paper as a survey analysis with theoretical conclusions.