Bioorganic & Medicinal Chemistry Letters, Feb 1, 2011
The A 1 adenosine receptor (A 1 AR) antagonist [ 18 F]cyclopentyl-3-(3-fluoropropyl)-1propylxanth... more The A 1 adenosine receptor (A 1 AR) antagonist [ 18 F]cyclopentyl-3-(3-fluoropropyl)-1propylxanthine ([ 18 F]CPFPX), used in imaging human brain A 1 ARs by PET, is stable in the brain but rapidly undergoes transformation into one major (M1) and several minor metabolites in blood. This report describes the synthesis of putative metabolites of CPFPX as standards for the identification of those metabolites. Analysis by (radio)HPLC revealed that extracts of human liver microsomes incubated with n.c.a.[ 18 F]CPFPX contained the major metabolite, M1, as well as radioactive metabolites corresponding to derivatives functionalized at the cyclopentyl moiety, but no N 1-despropyl species or metabolites resulting from functionalizations of the N 3-fluoropropyl chain. The putative metabolites displaced the binding of [ 3 H]CPFPX to the A 1 AR in pig brain cortex at K i s between 1.9 and 380 nM and the binding of [ 3 H]ZM 241385 to the A 2A AR in pig striatum at K i s greater than 180 nM. One metabolite, a derivative functionalized at the -position of the N 1propyl chain, showed high affinity (K i 2 nM) to and very good selectivity (> 9000) for the A 1 AR.
The importance of nitriles as a key class of chemicals with applications across the sciences is w... more The importance of nitriles as a key class of chemicals with applications across the sciences is widely appreciated. The natural world is an underappreciated source of chemically diverse nitriles. With this in mind, this review describes novel nitrile-containing molecules isolated from natural sources from 1998 to 2021, as well as a discussion of the biological activity of these compounds. This study gathers 192 molecules from varied origins across the plant, animal, and microbial worlds. Their biological activity is extremely diverse, with many potential medicinal applications.
Vitamin K1 (VitK1) and Vitamin K2 (VitK2), two important naturally occurring micronutrients in th... more Vitamin K1 (VitK1) and Vitamin K2 (VitK2), two important naturally occurring micronutrients in the VitK family, found, respectively, in green leafy plants and algae (VitK1) and animal and fermented foods (VitK2). The present review explores the multiple biological functions of VitK2 from recently published in vitro and in vivo studies, including promotion of osteogenesis, prevention of calcification, relief of menopausal symptoms, enhancement of mitochondrial energy release, hepato‐ and neuro‐protective effects, and possible use in treatment of coronavirus disease. The mechanisms of action associated with these biological effects are also explored. Overall, the findings presented here suggest that VitK, especially VitK2, is an important nutrient family for the normal functioning of human health. It acts on almost all major body systems and directly or indirectly participates in and regulates hundreds of physiological or pathological processes. However, as biological and clinical dat...
BackgroundEffective communication between pharmacists and patients is essential and improves heal... more BackgroundEffective communication between pharmacists and patients is essential and improves health outcomes. Simulated patients (SPs) are trained to reproduce real-life situations and can help pharmacy students to develop and adapt their communication skills in a safe, learner-centred environment. The aim of this research was to explore how SP and pharmacy student role-play supports communication training.MethodsA mixed methods realist evaluation approach was adopted to test an initial theory relating to SP role-play for pharmacy students. The intervention tested involved complex communication cases in a men’s and women’s health module in year three of a new MPharm programme. This SP session was the first such session, of the programme which exclusively focused on complex communication skills for the students. Data collected comprised video-recordings of both training and mock OSCE sessions, and from student focus groups. Communication videos were scored using the Explanation and P...
BackgroundThe COVID-19 pandemic triggered rapid, fundamental changes in how healthcare is deliver... more BackgroundThe COVID-19 pandemic triggered rapid, fundamental changes in how healthcare is delivered in communities, notably increased remote delivery of primary care. While the impact of these changes on medication safety are not yet fully understood, research conducted before the pandemic may provide evidence for possible consequences. This rapid review examines the published literature on medication safety incidents associated with the remote delivery of primary care.Objective(s)To examine the published literature on medication safety incidents associated with the remote delivery of primary care, with a focus on telemedicine and electronic prescribing.MethodsA rapid review was conducted according to the Cochrane Rapid Reviews Methods Group guidance. An electronic search was carried out on Embase and Medline (via PubMed) using key search terms “medication error”, “electronic prescribing”, “telemedicine” and “primary care”. Identified studies were synthesised narratively; reported m...
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
THESIS 7175The purpose of this thesis was the design, synthesis and pharmacological screening of ... more THESIS 7175The purpose of this thesis was the design, synthesis and pharmacological screening of a novel series of tetrahydronapthalene molecules for mast cell-stabilising activity. The introductory Chapter commences with a discussion of mast cells and basophils as key effectors of the allergic response. The molecular mechanisms through which these cells are activated and degranulated are discussed, together with a synopsis of the chemical mediators of allergy released from them, both upon degranulation and those synthesised de novo. The consequences of pathological activation of the allergic cascade are then outlined, with an overview of both currently available and investigational therapies for these conditions, with especial emphasis on molecules derived from natural sources. The rationale for the screening of the target molecules is introduced, with reference to previously tested indan molecules and dimers thereof, and the biological activities of indan and tetrahydronaphthalene molecules reported to date is reviewed. Chapter 1 concludes with a discussion of the various pharmacological models of allergic disease that are utilised in candidate drug screening programmes
Research in Social and Administrative Pharmacy, 2021
The impact of the COVID-19 pandemic on pharmacy education worldwide has been immense, affecting s... more The impact of the COVID-19 pandemic on pharmacy education worldwide has been immense, affecting students, educators and regulatory agencies. Pharmacy programmes have had to rapidly adapt in their delivery of education, maintaining standards while also ensuring the safety of all stakeholders. In this commentary, we describe the challenges, compromises and solutions adopted by our institution throughout the pandemic, the lessons learnt, adaptive measures taken, and strategies to develop and future-proof our curricula.
American Journal of Pharmaceutical Education, 2019
Objective. To design, deliver, and evaluate a National Pharmacy Internship Program that met the e... more Objective. To design, deliver, and evaluate a National Pharmacy Internship Program that met the educational requirements of pharmacy graduates to register as competent pharmacists and earned graduates a master's level degree. Methods. The National Pharmacy Internship Program was designed as a 12-month, full-time, blendedlearning, competency-based program leading to a master's degree. Intern performance was assessed academically and by pharmacy preceptor (tutor) appraisals. Interns who demonstrated competency were invited to sit for the Professional Registration Examination (PRE). Feasibility and performance were evaluated and a longitudinal approach allowed intern and preceptor views to be compared to the former preregistration year. Results. Overall performance in the PRE was good and relatively consistent with almost all interns proceeding to register as pharmacists. Interns believed that the program had enabled them to develop the knowledge, skills, and overall competencies required for future independent practice as a pharmacist. Preceptors considered the program to have built on prior learning and provided a sufficiently rounded experience for professional practice. Preceptors also stated that the program was an improved educational experience over the former, less structured, preregistration training. Conclusion. The National Pharmacy Internship Program was perceived to be an improvement on the previous preregistration year. The program quality assured pharmacy education outcomes at the entryto-practice level on a national basis, and uniquely recognized the students' accomplishment by awarding them a master's degree.
Background: The present study documents the ethnomedicinal knowledge among the traditional healer... more Background: The present study documents the ethnomedicinal knowledge among the traditional healers of the Pangkhua indigenous community of Bangladesh. The documented data from this area was quantitatively analyzed for the first time. We aimed to record ethnomedicinal information from both the traditional healers and also the elderly men and women of the community, in order to compile and document all available information concerning plant use and preserve it for the coming generations. We aimed to compare how already known species are used compared to elsewhere and particularly to highlight new ethnomedicinal plant species alongside their therapeutic use(s). Methods: All ethnomedicinal information was collected following established techniques. Open-ended and semistructured techniques were primarily utilized. Data was analyzed using different quantitative indices. The level of homogeneity between information provided by different informants was calculated using the Informant Consensus Factor. All recorded plant species are presented in tabular format, alongside corresponding ethnomedicinal usage information.
Congea tomentosa Roxb. (CT) is used as a medicinal plant by indigenous peoples of Bangladesh, but... more Congea tomentosa Roxb. (CT) is used as a medicinal plant by indigenous peoples of Bangladesh, but to date remains largely unexplored from a phytochemical or pharmacological perspective. In this study, the extracts of leaves, stems and flowers of CT were tested for antimicrobial activity 2 using the agar well diffusion and micro-dilution methods. Compared with leaf and flower extracts, the crude stem extract was the most effective against the tested microorganisms. Therefore, the crude stem extract was further subjected to sequential fractionation, with the petroleum ether and ethyl acetate extracts proving the most active against tested microorganisms. Using GC-MS analysis, 10 compounds were identified within the petroleum ether extract, all of which are known to the literature, and some/all of which may have contributed to the observed antimicrobial properties. Additionally, two compounds (β-amyrin and stigmasterol) were isolated from the ethyl acetate fraction and identified using mass spectrometry and NMR spectroscopy. Compound 2 (stigmasterol) displayed promising antimicrobial activity against tested microorganisms. Despite the ethnobotanical importance of CT, this work represents the first scientific report supporting its traditional use, and demonstrates that both the stem extract of this ethnomedicinal plant and the isolated compound 2 (stigmasterol) may offer potential as antimicrobials.
Mast cells play a critical role in type 1 hypersensitivity reactions. Indeed, mast cell mediators... more Mast cells play a critical role in type 1 hypersensitivity reactions. Indeed, mast cell mediators are implicated in many different conditions including allergic rhinitis, conjunctivitis, asthma, psoriasis, mastocytosis and the progression of many different cancers. Thus, there is intense interest in the development of agents which prevent mast cell mediator release or which inhibit the actions of such mediators once released into the environment of the cell. Much progress into the design of new agents has been made since the initial discovery of the mast cell stabilising properties of khellin from Ammi visnaga and the clinical approval of cromolyn sodium. This review critically examines the progress that has been made in the intervening years from the design of new agents that target a specific signalling event in the mast cell degranulation pathway to those agents which have been developed where the precise mechanism of action remains elusive. Particular emphasis is also placed on ...
Carriers are often an essential element of drug delivery, bestowing attributes to their cargo suc... more Carriers are often an essential element of drug delivery, bestowing attributes to their cargo such as biocompatibility, enhanced delivery, extended half-life and efficacy as well as mediating specific targeting at a tissue, cell or intracellular level. Liposomes and lipid-based carriers have been investigated for decades for this purpose, many achieving clinical approval including products such as Doxil™ and Myocet™. However, reports also indicate issues with the use of cationic lipids, toxicity in particular. It is important to consider that carrier or vector systems engineered to efficiently deliver a drug may not be inert. Large-scale compound screens are routinely carried out in the field of drug discovery; however less work has been done on harnessing high throughput methods for carrier material screening. Screening the interaction of drug carriers and materials with cells is particularly critical for the development of emerging therapies, including biomedicines, in order to facilitate the development of safe and efficient drug products. Herein, a range of liposomes of neutral, anionic and cationic charge and others that are surface-modified with mannose residues were screened for cell interaction, toxicity and immune reactivity in THP-1-derived macrophages using a high throughput format.
Bioorganic & Medicinal Chemistry Letters, Feb 1, 2011
The A 1 adenosine receptor (A 1 AR) antagonist [ 18 F]cyclopentyl-3-(3-fluoropropyl)-1propylxanth... more The A 1 adenosine receptor (A 1 AR) antagonist [ 18 F]cyclopentyl-3-(3-fluoropropyl)-1propylxanthine ([ 18 F]CPFPX), used in imaging human brain A 1 ARs by PET, is stable in the brain but rapidly undergoes transformation into one major (M1) and several minor metabolites in blood. This report describes the synthesis of putative metabolites of CPFPX as standards for the identification of those metabolites. Analysis by (radio)HPLC revealed that extracts of human liver microsomes incubated with n.c.a.[ 18 F]CPFPX contained the major metabolite, M1, as well as radioactive metabolites corresponding to derivatives functionalized at the cyclopentyl moiety, but no N 1-despropyl species or metabolites resulting from functionalizations of the N 3-fluoropropyl chain. The putative metabolites displaced the binding of [ 3 H]CPFPX to the A 1 AR in pig brain cortex at K i s between 1.9 and 380 nM and the binding of [ 3 H]ZM 241385 to the A 2A AR in pig striatum at K i s greater than 180 nM. One metabolite, a derivative functionalized at the -position of the N 1propyl chain, showed high affinity (K i 2 nM) to and very good selectivity (> 9000) for the A 1 AR.
The importance of nitriles as a key class of chemicals with applications across the sciences is w... more The importance of nitriles as a key class of chemicals with applications across the sciences is widely appreciated. The natural world is an underappreciated source of chemically diverse nitriles. With this in mind, this review describes novel nitrile-containing molecules isolated from natural sources from 1998 to 2021, as well as a discussion of the biological activity of these compounds. This study gathers 192 molecules from varied origins across the plant, animal, and microbial worlds. Their biological activity is extremely diverse, with many potential medicinal applications.
Vitamin K1 (VitK1) and Vitamin K2 (VitK2), two important naturally occurring micronutrients in th... more Vitamin K1 (VitK1) and Vitamin K2 (VitK2), two important naturally occurring micronutrients in the VitK family, found, respectively, in green leafy plants and algae (VitK1) and animal and fermented foods (VitK2). The present review explores the multiple biological functions of VitK2 from recently published in vitro and in vivo studies, including promotion of osteogenesis, prevention of calcification, relief of menopausal symptoms, enhancement of mitochondrial energy release, hepato‐ and neuro‐protective effects, and possible use in treatment of coronavirus disease. The mechanisms of action associated with these biological effects are also explored. Overall, the findings presented here suggest that VitK, especially VitK2, is an important nutrient family for the normal functioning of human health. It acts on almost all major body systems and directly or indirectly participates in and regulates hundreds of physiological or pathological processes. However, as biological and clinical dat...
BackgroundEffective communication between pharmacists and patients is essential and improves heal... more BackgroundEffective communication between pharmacists and patients is essential and improves health outcomes. Simulated patients (SPs) are trained to reproduce real-life situations and can help pharmacy students to develop and adapt their communication skills in a safe, learner-centred environment. The aim of this research was to explore how SP and pharmacy student role-play supports communication training.MethodsA mixed methods realist evaluation approach was adopted to test an initial theory relating to SP role-play for pharmacy students. The intervention tested involved complex communication cases in a men’s and women’s health module in year three of a new MPharm programme. This SP session was the first such session, of the programme which exclusively focused on complex communication skills for the students. Data collected comprised video-recordings of both training and mock OSCE sessions, and from student focus groups. Communication videos were scored using the Explanation and P...
BackgroundThe COVID-19 pandemic triggered rapid, fundamental changes in how healthcare is deliver... more BackgroundThe COVID-19 pandemic triggered rapid, fundamental changes in how healthcare is delivered in communities, notably increased remote delivery of primary care. While the impact of these changes on medication safety are not yet fully understood, research conducted before the pandemic may provide evidence for possible consequences. This rapid review examines the published literature on medication safety incidents associated with the remote delivery of primary care.Objective(s)To examine the published literature on medication safety incidents associated with the remote delivery of primary care, with a focus on telemedicine and electronic prescribing.MethodsA rapid review was conducted according to the Cochrane Rapid Reviews Methods Group guidance. An electronic search was carried out on Embase and Medline (via PubMed) using key search terms “medication error”, “electronic prescribing”, “telemedicine” and “primary care”. Identified studies were synthesised narratively; reported m...
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
THESIS 7175The purpose of this thesis was the design, synthesis and pharmacological screening of ... more THESIS 7175The purpose of this thesis was the design, synthesis and pharmacological screening of a novel series of tetrahydronapthalene molecules for mast cell-stabilising activity. The introductory Chapter commences with a discussion of mast cells and basophils as key effectors of the allergic response. The molecular mechanisms through which these cells are activated and degranulated are discussed, together with a synopsis of the chemical mediators of allergy released from them, both upon degranulation and those synthesised de novo. The consequences of pathological activation of the allergic cascade are then outlined, with an overview of both currently available and investigational therapies for these conditions, with especial emphasis on molecules derived from natural sources. The rationale for the screening of the target molecules is introduced, with reference to previously tested indan molecules and dimers thereof, and the biological activities of indan and tetrahydronaphthalene molecules reported to date is reviewed. Chapter 1 concludes with a discussion of the various pharmacological models of allergic disease that are utilised in candidate drug screening programmes
Research in Social and Administrative Pharmacy, 2021
The impact of the COVID-19 pandemic on pharmacy education worldwide has been immense, affecting s... more The impact of the COVID-19 pandemic on pharmacy education worldwide has been immense, affecting students, educators and regulatory agencies. Pharmacy programmes have had to rapidly adapt in their delivery of education, maintaining standards while also ensuring the safety of all stakeholders. In this commentary, we describe the challenges, compromises and solutions adopted by our institution throughout the pandemic, the lessons learnt, adaptive measures taken, and strategies to develop and future-proof our curricula.
American Journal of Pharmaceutical Education, 2019
Objective. To design, deliver, and evaluate a National Pharmacy Internship Program that met the e... more Objective. To design, deliver, and evaluate a National Pharmacy Internship Program that met the educational requirements of pharmacy graduates to register as competent pharmacists and earned graduates a master's level degree. Methods. The National Pharmacy Internship Program was designed as a 12-month, full-time, blendedlearning, competency-based program leading to a master's degree. Intern performance was assessed academically and by pharmacy preceptor (tutor) appraisals. Interns who demonstrated competency were invited to sit for the Professional Registration Examination (PRE). Feasibility and performance were evaluated and a longitudinal approach allowed intern and preceptor views to be compared to the former preregistration year. Results. Overall performance in the PRE was good and relatively consistent with almost all interns proceeding to register as pharmacists. Interns believed that the program had enabled them to develop the knowledge, skills, and overall competencies required for future independent practice as a pharmacist. Preceptors considered the program to have built on prior learning and provided a sufficiently rounded experience for professional practice. Preceptors also stated that the program was an improved educational experience over the former, less structured, preregistration training. Conclusion. The National Pharmacy Internship Program was perceived to be an improvement on the previous preregistration year. The program quality assured pharmacy education outcomes at the entryto-practice level on a national basis, and uniquely recognized the students' accomplishment by awarding them a master's degree.
Background: The present study documents the ethnomedicinal knowledge among the traditional healer... more Background: The present study documents the ethnomedicinal knowledge among the traditional healers of the Pangkhua indigenous community of Bangladesh. The documented data from this area was quantitatively analyzed for the first time. We aimed to record ethnomedicinal information from both the traditional healers and also the elderly men and women of the community, in order to compile and document all available information concerning plant use and preserve it for the coming generations. We aimed to compare how already known species are used compared to elsewhere and particularly to highlight new ethnomedicinal plant species alongside their therapeutic use(s). Methods: All ethnomedicinal information was collected following established techniques. Open-ended and semistructured techniques were primarily utilized. Data was analyzed using different quantitative indices. The level of homogeneity between information provided by different informants was calculated using the Informant Consensus Factor. All recorded plant species are presented in tabular format, alongside corresponding ethnomedicinal usage information.
Congea tomentosa Roxb. (CT) is used as a medicinal plant by indigenous peoples of Bangladesh, but... more Congea tomentosa Roxb. (CT) is used as a medicinal plant by indigenous peoples of Bangladesh, but to date remains largely unexplored from a phytochemical or pharmacological perspective. In this study, the extracts of leaves, stems and flowers of CT were tested for antimicrobial activity 2 using the agar well diffusion and micro-dilution methods. Compared with leaf and flower extracts, the crude stem extract was the most effective against the tested microorganisms. Therefore, the crude stem extract was further subjected to sequential fractionation, with the petroleum ether and ethyl acetate extracts proving the most active against tested microorganisms. Using GC-MS analysis, 10 compounds were identified within the petroleum ether extract, all of which are known to the literature, and some/all of which may have contributed to the observed antimicrobial properties. Additionally, two compounds (β-amyrin and stigmasterol) were isolated from the ethyl acetate fraction and identified using mass spectrometry and NMR spectroscopy. Compound 2 (stigmasterol) displayed promising antimicrobial activity against tested microorganisms. Despite the ethnobotanical importance of CT, this work represents the first scientific report supporting its traditional use, and demonstrates that both the stem extract of this ethnomedicinal plant and the isolated compound 2 (stigmasterol) may offer potential as antimicrobials.
Mast cells play a critical role in type 1 hypersensitivity reactions. Indeed, mast cell mediators... more Mast cells play a critical role in type 1 hypersensitivity reactions. Indeed, mast cell mediators are implicated in many different conditions including allergic rhinitis, conjunctivitis, asthma, psoriasis, mastocytosis and the progression of many different cancers. Thus, there is intense interest in the development of agents which prevent mast cell mediator release or which inhibit the actions of such mediators once released into the environment of the cell. Much progress into the design of new agents has been made since the initial discovery of the mast cell stabilising properties of khellin from Ammi visnaga and the clinical approval of cromolyn sodium. This review critically examines the progress that has been made in the intervening years from the design of new agents that target a specific signalling event in the mast cell degranulation pathway to those agents which have been developed where the precise mechanism of action remains elusive. Particular emphasis is also placed on ...
Carriers are often an essential element of drug delivery, bestowing attributes to their cargo suc... more Carriers are often an essential element of drug delivery, bestowing attributes to their cargo such as biocompatibility, enhanced delivery, extended half-life and efficacy as well as mediating specific targeting at a tissue, cell or intracellular level. Liposomes and lipid-based carriers have been investigated for decades for this purpose, many achieving clinical approval including products such as Doxil™ and Myocet™. However, reports also indicate issues with the use of cationic lipids, toxicity in particular. It is important to consider that carrier or vector systems engineered to efficiently deliver a drug may not be inert. Large-scale compound screens are routinely carried out in the field of drug discovery; however less work has been done on harnessing high throughput methods for carrier material screening. Screening the interaction of drug carriers and materials with cells is particularly critical for the development of emerging therapies, including biomedicines, in order to facilitate the development of safe and efficient drug products. Herein, a range of liposomes of neutral, anionic and cationic charge and others that are surface-modified with mannose residues were screened for cell interaction, toxicity and immune reactivity in THP-1-derived macrophages using a high throughput format.
Uploads
Papers by James Barlow