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1.
BMJ Open ; 14(5): e081518, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38749689

RESUMO

OBJECTIVES: It is important that allied health professionals (AHPs) are prepared for clinical practice from the very start of their working lives to provide quality care for patients, for their personal well-being and for retention of the workforce. The aim of this study was to understand how well newly qualified AHPs were prepared for practice in the UK. DESIGN: Systematic review. DATA SOURCES: Embase, MEDLINE, CINAHL, ERIC and BEI were searched from 2012 to 2024. Grey literature searching and citation chasing were also conducted. ELIGIBILITY CRITERIA: We included primary studies reporting the preparedness for practice of UK graduates across 15 professions; all study types; participants included graduates who were up to 2 years postgraduation, their supervisors, trainers, practice educators and employers; and all outcome measures. DATA EXTRACTION AND SYNTHESIS: A standardised data extraction form was used. Studies were quality assessed using the Quality Appraisal for Diverse Studies tool. 10% of articles were independently double-screened, extracted and quality assessed; 90% was completed by one researcher. RESULTS: 14 reports were included (9 qualitative, 3 mixed-method and 2 quantitative). Six papers focused on radiographers, three on a mixture of professions, two on paramedics, and one each on physiotherapists, clinical psychologists and orthotists. An important finding of the review is the paucity and low-medium quality of research on the topic. The narrative synthesis tentatively suggests that graduates are adequately prepared for practice with different professions having different strengths and weaknesses. Common areas of underpreparedness across the professions were responsibility and decision-making, leadership and research. Graduates were generally well prepared in terms of their knowledge base. CONCLUSION: High-quality in-depth research is urgently needed across AHPs to elucidate the specific roles, their nuances and the areas of underpreparedness. Further work is also needed to understand the transition into early clinical practice, ongoing learning opportunities through work, and the supervision and support structures in place. PROSPERO REGISTRATION NUMBER: CRD42022382065.


Assuntos
Pessoal Técnico de Saúde , Competência Clínica , Pessoal Técnico de Saúde/educação , Humanos , Reino Unido
2.
J Pastoral Care Counsel ; 77(1): 51-63, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36262109

RESUMO

Christian clergy are at risk of experiencing the negative impacts of role-related stress and adversity, especially burnout. The findings reported in this article were derived from a Canadian mix-methods study that collected data through an online survey with 519 clerics, 13 one-on-one interviews, and interpretation panels. Adversity themes identified related to workload, expectations, isolation, and personal challenges with various subthemes for each. These findings are relevant to those providing care to clergy by providing insights into the challenges they face.


Assuntos
Esgotamento Profissional , Assistência Religiosa , Humanos , Clero , Assistência Religiosa/métodos , Canadá , Cristianismo
3.
J Spec Pediatr Nurs ; 28(1): e12402, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36463504

RESUMO

PURPOSE: In pediatric care settings, family-centered care (FCC) is an integral way to ensure family involvement in their child's care and has been known to improve health outcomes and families' psychosocial well-being. Similarly, nursing presence is deemed beneficial in the formation of authentic nurse-patient relationships and is known to facilitate healing and improve satisfaction for the patient and their family. The objective of this article is to explore how nursing presence supports FCC by closely examining the four concepts of FCC as described by Institute for Patient- and Family-Centered Care: dignity and respect, information sharing, participation, and collaboration. A case study is also presented to demonstrate how nursing presence can be applied in FCC, when caring for a pediatric oncology patient. CONCLUSION: Nursing presence is essential in FCC since it plays a key role in the formation of relationships, a fundamental element in the four concepts. Attributes of nursing presence can be interwoven in the FCC framework and have positive clinical, social, and emotional outcomes for the patient and family. Although literature has explored associations between FCC and nursing presence, there is need for more scientific research to justify this argument to support the improvement of quality of family nursing care and strengthen the FCC model. PRACTICE IMPLICATIONS: The four concepts of FCC lay a foundation for a model of care that can be enhanced by nursing presence, potentially providing a remedy for depersonalization of healthcare by improving nurse patient relationships in pediatric care settings. Nursing presence becomes less ambiguous when enacted in a FCC framework, revealing attributes that may be cultivated in family nursing to improve therapeutic relationships among nurses and family caregivers.


Assuntos
Neoplasias , Enfermeiras e Enfermeiros , Criança , Humanos , Atenção à Saúde , Cuidadores , Neoplasias/terapia , Assistência Centrada no Paciente , Enfermagem Pediátrica
4.
Pastoral Psychol ; 71(5): 597-613, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36032776

RESUMO

Clergy play significant leadership, educational, and caregiving roles in society. However, burnout is a concern for the clergy profession, those they serve, and their families. Effects include decreased ministry effectiveness, lower sense of personal accomplishment in their role, and negative impacts on quality of family life and relationships. Given these risks, knowledge of the nature of Christian clergy's current resilience and well-being in Canada may provide valuable intelligence to mitigate these challenges. In summary, the purpose of this research was to describe and analyze the status of clergy resilience and well-being in Canada, together with offering focused insights. Resilience and well-being surveys used by the co-authors with educators and nurses were adapted for use in this study. This instrument was developed to gain insight into baseline patterns of resilience and well-being and included questions across seven sections: (1) demographic information. (2) health status, (3) professional quality of life, (4) Cantril Well-Being Scale, (5) Ego-Resiliency Scale, (6) Grit Scale, and (7) open-ended questions. The findings provided valuable insights into clergy well-being and resilience that can benefit individual clerics, educational institutions, denominations, and congregations. The participants' current resilience and well-being included high levels of resiliency, moderate grit, and satisfaction with health and wellness. Other significant findings included the impact of congregational flourishing and age. This study found that clergy well-being and resilience was doing well despite the increased adversity of the COVID-19 pandemic. Implications of this study are that clerics may need unique supports based on their age and also whether they serve in a congregation they perceive as flourishing.

5.
J Pediatr Nurs ; 66: 86-94, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35687929

RESUMO

BACKGROUND: Nursing presence has been viewed as a valuable way to create therapeutic relationships and has been linked to better health outcomes for patients and families. However, whether nursing presence can be described and how parents in pediatric oncology experience this phenomenon remains unanswered. Therefore, the purpose of this study was to explore how parents of children with cancer describe and experience nursing presence. METHODS: This study used Giorgi's phenomenological approach to explore nursing presence as experienced by parents of children with cancer. Ten participants from a pediatric oncology clinic in Canada were interviewed. Giorgi's approach was used to analyze these data. FINDINGS: Based upon participants' descriptions, a structure of nursing presence emerged which included six constituent features: An attitude of presence, a source of encouragement, clinical experience and expertise, therapeutic communication, family involvement, and a sense of home away from home. Most notably, nursing presence as experienced by parents was characterized by the 'being' and 'doing' of presence which were equally important. CONCLUSION: The experiences described by parents provided rich and nuanced insights into what it meant to experience nursing presence in a pediatric oncology setting. This study provides a structure for this meaning making and expounds on its constituent features, describing what nursing presence resembles when experienced by parents of children with cancer. PRACTICE IMPLICATIONS: This study informs nursing practice, policy, and education in ways that are likely to enhance care and the subsequent well-being of pediatric oncology patients and families.


Assuntos
Neoplasias , Pais , Atitude , Criança , Comunicação , Humanos , Oncologia , Enfermagem Oncológica
6.
J Pastoral Care Counsel ; 76(3): 210-223, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35435069

RESUMO

Resilience is a helpful construct when considering how to support clergy well-being. The purpose of this study was to gain knowledge about clergy resilience, specifically those resources that clergy perceived had supported their professional resilience. The study gave attention to aspects of preservice training and professional development that helped to foster clergy resilience and initiatives that clergy desired to further support their resilience. Clergy reported multiple resources that supported their resilience including supports for spiritual life, relational supports, personal aspects, and organizational practices. Spiritual dimensions of support for resilience were prominent for clergy, especially the centrality of calling to ministry, theological meaning-making, and relationship with God. Participants also revealed helpful aspects of preservice training and professional development. Aspects of preservice training included rigorous discernment and screening of their callings and the inclusion of required practices, such as spiritual direction or mentorship. Aspects of professional development included a variety of skill development opportunities, lifelong learning, conferences, and networking with peers. Participants reported their desire for initiatives that included more wellness opportunities and an increased organizational prioritization of clergy wellness.


Assuntos
Clero , Assistência Religiosa , Humanos
8.
Nurse Educ Pract ; 51: 102978, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33571805

RESUMO

Undergraduate nursing students report high levels of stress which can negatively impact their overall wellness, and their academic and clinical performance. Despite this knowledge, there are few studies that have examined the well-being of nursing students and their ability to demonstrate resilience. Therefore, the purpose of this exploratory study was to examine resilience and wellness, together with the key factors that promote a well-being in nursing students from mid-western Canadian university. The sample of 196 undergraduate nursing students completed an online Nursing Well-being and Resilience Survey. Findings indicated that most nursing students had good health; however, many presented with anxiety and/or depression and a decreased sense of wellness in the physical, spiritual, and emotional domain. Other significant findings included participants >26 years old having lower burnout scores, higher ego-resilience and well-being scores compared to students ages 20 to 25; and, 2) there were differences between campus locations in terms of Professional Quality of life (compassion satisfaction, burnout, and traumatic stress) and sense of well-being. Understanding how resilience and wellness are influenced throughout the nursing program is a first step in developing targeted wellness initiatives for different nursing student populations.


Assuntos
Esgotamento Profissional , Bacharelado em Enfermagem , Resiliência Psicológica , Estudantes de Enfermagem , Adulto , Canadá , Humanos , Qualidade de Vida , Adulto Jovem
9.
Vet Pathol ; 58(1): 114-122, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33205699

RESUMO

Despite previous detection of Chlamydia pecorum in sporadic ovine abortions, published descriptions of naturally occurring infections with fetoplacental lesions are lacking. This report provides the first descriptions of severe necrosuppurative chorionitis with vasculitis, and fetal pyelonephritis and enteritis in late-term abortions of maiden ewes. Chlamydial infection was detected using a Chlamydia genus-specific qPCR (quantitative polymerase chain reaction) on tissue extracts from 3 fetuses. C. pecorum was identified using a targeted qPCR assay, which also determined infectious load within fetal tissues. The presence of viable C. pecorum in fetal samples was confirmed by cell culture. Multilocus sequence typing (MLST) data indicated that the C. pecorum strains from each fetus were identical and of sequence type (ST) 23. Chlamydia sp. immunohistochemistry showed strong positive immunolabeling of fetoplacental lesions. Other infectious abortigenic agents were excluded with specific testing. This report confirms C. pecorum as a likely cause of ovine abortion and provides the first descriptions of associated fetoplacental lesions in naturally infected sheep.


Assuntos
Infecções por Chlamydia , Chlamydia , Doenças dos Ovinos , Animais , Chlamydia/genética , Infecções por Chlamydia/veterinária , Feminino , Tipagem de Sequências Multilocus/veterinária , Gravidez , Ovinos
10.
PLoS One ; 15(9): e0238697, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970694

RESUMO

Niemann-Pick type C disease is a lysosomal storage disease affecting primarily the nervous system that results in premature death. Here we present the first report and investigation of Niemann-Pick type C disease in Australian Angus/Angus-cross calves. After a preliminary diagnosis of Niemann-Pick type C, samples from two affected calves and two obligate carriers were analysed using single nucleotide polymorphism genotyping and homozygosity mapping, and NPC1 was considered as a positional candidate gene. A likely causal missense variant on chromosome 24 in the NPC1 gene (NM_174758.2:c.2969C>G) was identified by Sanger sequencing of cDNA. SIFT analysis, protein alignment and protein modelling predicted the variant to be deleterious to protein function. Segregation of the variant with disease was confirmed in two additional affected calves and two obligate carrier dams. Genotyping of 403 animals from the original herd identified an estimated allele frequency of 3.5%. The Niemann-Pick type C phenotype was additionally confirmed via biochemical analysis of Lysotracker Green, cholesterol, sphingosine and glycosphingolipids in fibroblast cell cultures originating from two affected calves. The identification of a novel missense variant for Niemann-Pick type C disease in Angus/Angus-cross cattle will enable improved breeding and management of this disease in at-risk populations. The results from this study offer a unique opportunity to further the knowledge of human Niemann-Pick type C disease through the potential availability of a bovine model of disease.


Assuntos
Doença de Niemann-Pick Tipo C/genética , Doença de Niemann-Pick Tipo C/patologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Bovinos , Células Cultivadas , Toxina da Cólera/metabolismo , Colesterol/metabolismo , DNA Complementar/genética , Modelos Animais de Doenças , Fibroblastos/patologia , Gangliosídeo G(M1)/metabolismo , Homozigoto , Mutação/genética , Proteína C1 de Niemann-Pick/química , Proteína C1 de Niemann-Pick/genética , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Polissacarídeos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
11.
BMC Med Educ ; 17(1): 169, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-28927466

RESUMO

BACKGROUND: With current emphasis on leadership in medicine, this study explores Goleman's leadership styles of medical education leaders at different hierarchical levels and gain insight into factors that contribute to the appropriateness of practices. METHODS: Forty two leaders (28 first-level with limited formal authority, eight middle-level with wider program responsibility and six senior- level with higher organizational authority) rank ordered their preferred Goleman's styles and provided comments. Eight additional senior leaders were interviewed in-depth. Differences in ranked styles within groups were determined by Friedman tests and Wilcoxon tests. Based upon style descriptions, confirmatory template analysis was used to identify Goleman's styles for each interviewed participant. Content analysis was used to identify themes that affected leadership styles. RESULTS: There were differences in the repertoire and preferred styles at different leadership levels. As a group, first-level leaders preferred democratic, middle-level used coaching while the senior leaders did not have one preferred style and used multiple styles. Women and men preferred democratic and coaching styles respectively. The varied use of styles reflected leadership conceptualizations, leader accountabilities, contextual adaptations, the situation and its evolution, leaders' awareness of how they themselves were situated, and personal preferences and discomfort with styles. The not uncommon use of pace-setting and commanding styles by senior leaders, who were interviewed, was linked to working with physicians and delivering quickly on outcomes. CONCLUSIONS: Leaders at different levels in medical education draw from a repertoire of styles. Leadership development should incorporate learning of different leadership styles, especially at first- and mid-level positions.


Assuntos
Educação Médica , Educação Profissionalizante/normas , Pessoal de Saúde/normas , Liderança , Comportamento Cooperativo , Pessoal de Saúde/educação , Humanos , Projetos Piloto
12.
Plant Physiol ; 170(4): 1917-28, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26864017

RESUMO

Here, we report a form of oligonucleotide-directed mutagenesis for precision genome editing in plants that uses single-stranded oligonucleotides (ssODNs) to precisely and efficiently generate genome edits at DNA strand lesions made by DNA double strand break reagents. Employing a transgene model in Arabidopsis (Arabidopsis thaliana), we obtained a high frequency of precise targeted genome edits when ssODNs were introduced into protoplasts that were pretreated with the glycopeptide antibiotic phleomycin, a nonspecific DNA double strand breaker. Simultaneous delivery of ssODN and a site-specific DNA double strand breaker, either transcription activator-like effector nucleases (TALENs) or clustered, regularly interspaced, short palindromic repeats (CRISPR/Cas9), resulted in a much greater targeted genome-editing frequency compared with treatment with DNA double strand-breaking reagents alone. Using this site-specific approach, we applied the combination of ssODN and CRISPR/Cas9 to develop an herbicide tolerance trait in flax (Linum usitatissimum) by precisely editing the 5'-ENOLPYRUVYLSHIKIMATE-3-PHOSPHATE SYNTHASE (EPSPS) genes. EPSPS edits occurred at sufficient frequency that we could regenerate whole plants from edited protoplasts without employing selection. These plants were subsequently determined to be tolerant to the herbicide glyphosate in greenhouse spray tests. Progeny (C1) of these plants showed the expected Mendelian segregation of EPSPS edits. Our findings show the enormous potential of using a genome-editing platform for precise, reliable trait development in crop plants.


Assuntos
3-Fosfoshikimato 1-Carboxiviniltransferase/genética , Antibacterianos/farmacologia , Arabidopsis/genética , Endonucleases/metabolismo , Edição de Genes , Engenharia Genética , Genoma de Planta , Oligonucleotídeos/metabolismo , Adaptação Fisiológica/efeitos dos fármacos , Alelos , Arabidopsis/efeitos dos fármacos , Sequência de Bases , Sistemas CRISPR-Cas/genética , Linho/genética , Loci Gênicos , Glicina/análogos & derivados , Glicina/toxicidade , Glicopeptídeos/farmacologia , Proteínas de Fluorescência Verde/metabolismo , Plantas Geneticamente Modificadas , Protoplastos/efeitos dos fármacos , Protoplastos/metabolismo , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/metabolismo , Glifosato
13.
Plant Biotechnol J ; 14(2): 496-502, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26503400

RESUMO

Differences in gene sequences, many of which are single nucleotide polymorphisms, underlie some of the most important traits in plants. With humanity facing significant challenges to increase global agricultural productivity, there is an urgent need to accelerate the development of these traits in plants. oligonucleotide-directed mutagenesis (ODM), one of the many tools of Cibus' Rapid Trait Development System (RTDS(™) ) technology, offers a rapid, precise and non-transgenic breeding alternative for trait improvement in agriculture to address this urgent need. This review explores the application of ODM as a precision genome editing technology, with emphasis on using oligonucleotides to make targeted edits in plasmid, episomal and chromosomal DNA of bacterial, fungal, mammalian and plant systems. The process of employing ODM by way of RTDS technology has been improved in many ways by utilizing a fluorescence conversion system wherein a blue fluorescent protein (BFP) can be changed to a green fluorescent protein (GFP) by editing a single nucleotide of the BFP gene (CAC→TAC; H66 to Y66). For example, dependent on oligonucleotide length, applying oligonucleotide-mediated technology to target the BFP transgene in Arabidopsis thaliana protoplasts resulted in up to 0.05% precisely edited GFP loci. Here, the development of traits in commercially relevant plant varieties to improve crop performance by genome editing technologies such as ODM, and by extension RTDS, is reviewed.


Assuntos
Edição de Genes/métodos , Mutagênese Sítio-Dirigida/métodos , Oligonucleotídeos/genética , Conversão Gênica , Padrões de Herança/genética , Plantas/genética
14.
J Med Chem ; 58(21): 8413-26, 2015 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-26460788

RESUMO

Identification of singleton P2X7 inhibitor 1 from HTS gave a pharmacophore that eventually turned into potential clinical candidates 17 and 19. During development, a number of issues were successfully addressed, such as metabolic stability, plasma stability, GSH adduct formation, and aniline mutagenicity. Thus, careful modification of the molecule, such as conversion of the 1,4-dihydropyridinone to the 1,2-dihydropyridinone system, proper substitution at C-5″, and in some cases addition of fluorine atoms to the aniline ring allowed for the identification of a novel class of potent P2X7 inhibitors suitable for evaluating the role of P2X7 in inflammatory, immune, neurologic, or musculoskeletal disorders.


Assuntos
Antagonistas do Receptor Purinérgico P2X/química , Antagonistas do Receptor Purinérgico P2X/farmacologia , Piridonas/química , Piridonas/farmacologia , Receptores Purinérgicos P2X7/metabolismo , Compostos de Anilina/química , Compostos de Anilina/farmacologia , Halogenação , Humanos
15.
Healthc Policy ; 10(3): 23-31, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25947031

RESUMO

Leadership has a renewed focus in healthcare, and physicians are being increasingly involved in a range of leadership roles. The aim of this paper is to discuss several dualities that exert tensions at the systems and individual levels. Although oppositional, the common dualities of physician leadership are not mutually exclusive but represent a complex, dynamic and interdependent relationship, often coexisting with each other and exerting tensions in multiple dimensions. The authors contend that a dialectic understanding--instead of either/or or finding a middle ground--of the opposite poles of these dualities allows for generating meaningful leadership perspectives and choices.


Assuntos
Atenção à Saúde/organização & administração , Liderança , Papel do Médico , Canadá , Humanos
16.
J Spec Pediatr Nurs ; 18(3): 221-32, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23822846

RESUMO

PURPOSE: The purpose of this study was to explore the details of the experiences and meanings that adolescents associate with spirituality. DESIGN AND METHODS: This exploratory qualitative study used focus group discussions to uncover the experiences of 22 adolescents ages 16-19 years from two midwestern Canadian high schools. RESULTS: Three themes emerged: understandings of spirituality, the influence of spirituality on wellness, and the moderating influences of spirituality. PRACTICE IMPLICATIONS: The unique stories and experiences of this study's participants provide nurses with some possible starting points and ideas for dialogue related to spirituality with their adolescent clients.


Assuntos
Psicologia do Adolescente , Espiritualidade , Adolescente , Canadá , Feminino , Grupos Focais , Humanos , Masculino , Pesquisa Qualitativa , Adulto Jovem
17.
Issues Compr Pediatr Nurs ; 36(1-2): 17-36, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23600570

RESUMO

The purpose of this article is to present findings from two parallel qualitative studies that used focus groups to explore adolescent views of psychological wellness and healthy bodies. Nine focus groups were held with 46 adolescents aged 16-19 years from two Mid-Western Canadian high schools. Both studies were designed with an interpretive humanist perspective and then a 6-step thematic approach was used to analyze the data. Common themes emerging in the focus group discussions in both studies included the negative impact of media on adolescent body image and pressure to conform to the Western views of physical appearance. These findings illustrate the need for nurses to understand the influence of the media on adolescents' views of their body image and to incorporate protocols for assessment, education, and counseling of adolescents on the healthy usage of media into their pediatric clinical practice. Through consistent participation in the development and implementation of health policies, nurses play a critical role in supporting adolescents to develop healthy views of body image.


Assuntos
Atitude Frente a Saúde , Imagem Corporal , Meios de Comunicação de Massa , Adolescente , Feminino , Grupos Focais , Humanos , Masculino , Adulto Jovem
18.
Pediatr Nurs ; 38(6): 320-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23362631

RESUMO

This article presents and explains a "Framework for Exploring Adolescent Wellness" and outlines a research approach used to explore adolescent wellness specific to the discipline of nursing. The "Framework for Exploring Adolescent Wellness" assessed the concept of wellness through the perceptions of youth and sought to explain the relationship between adolescent well-being and development. A wellness survey was used to collect data from 280 youth, 16 to 20 years old, in two Western Canadian high schools. Their perceptions of wellness meant more to them than regular physical activity and healthy eating. The majority of youth suggested that psychological (89%), social (85%), and physical (80%) development made the most significant contribution to adolescent wellness. Slightly more than half the youth felt that spirituality (53%) contributed to their sense of wellness. These research findings indicate the need for an approach to adolescent nursing care that includes a high priority and greater visibility to the practice and philosophy of wellness.


Assuntos
Desenvolvimento do Adolescente , Atitude Frente a Saúde , Promoção da Saúde/métodos , Avaliação em Enfermagem/métodos , Adolescente , Canadá , Feminino , Nível de Saúde , Humanos , Masculino , Modelos Teóricos , Enfermagem Pediátrica , Autoimagem , Ajustamento Social , Espiritualidade , Adulto Jovem
19.
Bioorg Med Chem Lett ; 21(1): 423-6, 2011 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-21074992
20.
Bioorg Med Chem Lett ; 21(1): 417-22, 2011 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-21074993

RESUMO

A novel series of (E)-1-((2-(1-methyl-1H-imidazol-5-yl) quinolin-4-yl) methylene) thiosemicarbazides was discovered as potent inhibitors of IKKß. In this Letter we document our early efforts at optimization of the quinoline core, the imidazole and the semithiocarbazone moiety. Most potency gains came from substitution around the 6- and 7-positions of the quinoline ring. Replacement of the semithiocarbazone with a semicarbazone decreased potency but led to some measurable exposure.


Assuntos
Quinase I-kappa B/antagonistas & inibidores , Inibidores de Proteínas Quinases/química , Semicarbazidas/química , Animais , Cães , Feminino , Ensaios de Triagem em Larga Escala , Quinase I-kappa B/metabolismo , Masculino , Microssomos/metabolismo , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacocinética , Quinolinas/química , Ratos , Semicarbazidas/síntese química , Semicarbazidas/farmacocinética , Relação Estrutura-Atividade
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