Natural products containing the nitrile functional group and their biological activities

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

The experiences of migrant pharmacists: a phenomenographical study

Objectives: To understand the experiences of migrant pharmacists in Ireland as they applied for recognition of their qualifications and registration with the national accrediting body. Methods: Semi structured interviews were conducted with eight participants recruited using purposive sampling. Interview transcripts were subject to a phenomenographic study using a stepwise, inductive approach. Results: Data analysis led to the development of a number of categories or descriptions of understanding that provided insight into the ways that participants experienced and conceptualised the phenomenon under study. Five categories of description were identified. These are (1) the migrator, (2) the navigator, (3) the student again, and (4) the registrant. For some, an additional category, (5) the mentee, was experienced. Within these categories, variation in participants' experiences was explored. Conclusions: Participants reported a variety of reasons for migration, and upon embarking on the process, applicants were required to take on a variety of roles, with variation within each role dependent on a number of personal and external factors. Applicants faced personal, administrative, experiential and regulatory hurdles prior to registration, all of which should inform the development of future iterations of this and similar processes.</p

Isolation of erythrinan alkaloids from the leaves and flowers of Erythrina speciosa.

In this paper, we describe the extraction of three alkaloids from the leaves and flowers of Erythrina speciosa, a plant documented in the literature to possess a range of potential medicinal applications. Two alkaloids were isolated from both leaves and flowers, with erythrartine being isolated from both plant parts. In agreement with the literature, we also isolated erysotrine from the flowers. The second alkaloid isolated from the leaves, and reported in this species for the first time, was (+)-11β-hydroxyerysotramidine

Design, synthesis and evaluation of novel 2,2-dimethyl-2,3-dihydroquinolin-4(1H)-one based chalcones as cytotoxic agents

We designed and synthesised a series of novel chalcones, incorporating the heterocyclic framework of 2,2-dimethyl-2,3-dihydro-4(1H)-quinolinone, which was prepared via Sonogashira coupling of a substituted orthoaniline under aqueous conditions using Pd catalysis followed by acid-mediated cyclisation. The compounds were screened against the NCI-N87 and DLD-1 cancer cell lines, with most compounds showing low micromolar cytotoxic activity. </p

Evaluation of the type and frequency of extemporaneous formulations dispensed in hospital and community pharmacies

Background: Extemporaneous compounding is practiced globally by pharmacists to allow for dispensing of personalised doses of medicinal products not commercially available. Extemporaneous compounding must result in a product which is safe and effective. However, data on formulation and expiry of extemporaneous products may not be readily available. Pharmacists access various resources including compounding databases to obtain information on composition, preparation, and expiry of extemporaneous preparations. Objectives: The aim of this study was to evaluate the type and frequency of extemporaneous compounding in hospital and community pharmacies in the Republic of Ireland (ROI) and to obtain contemporary information on compounding practices and resources used. Methods: All community and hospital pharmacists registered with the Pharmaceutical Society of Ireland, were invited to participate in an on-line survey. The study was approved by the Royal College of Surgeons in Ireland (RCSI) research ethics committee. Results: A total of 202 pharmacists responded to the survey, of which 145 were community-based, 52 hospital-based, and 5 practicing in both. On average, hospital and community pharmacists (n = 138) dispensed Conclusions: The results of this study show that extemporaneous compounding is still practiced in hospital and community pharmacies in the ROI. The limited response of 4.6% obtained may reflect that extemporaneous compounding is concentrated in a relatively small number of pharmacies. There remains a clinical need for extemporaneous products in the ROI and extemporaneous compounding continues to be an invaluable skillset for pharmacists.</p

Medical Students' Knowledge, Perceptions, and Interest in Complementary and Alternative Medicine.

Abstract Background: Complementary and alternative medicine (CAM) is a growing industry in the health care system. In Ireland, to date there has not been a study that evaluates the knowledge of, interest in, and attitude of Irish medical students toward CAM. Objectives: This research can serve as a pilot study to inform Irish medical schools on the need to introduce CAM into the medical curriculum. Materials and Methods: The survey instrument was a modified design based on previously published studies carried out in other geographical areas. All medical students within the undergraduate and graduate entry programs (GEP) at the Royal College of Surgeons in Ireland were invited to participate in the study. SPSS software was used to analyze the results of the questionnaires. Results: The survey completion rate was 20.1%. A majority of students (78.4%) thought that CAM knowledge is important for their future career as physicians. Approximately 65% of students reported that they have not acquired sufficient knowledge about CAM from medical school, and 50.2% of students believe CAM should be incorporated into the medical curriculum. Preclinical years (49.4%) were suggested as the most appropriate time to learn about CAM. Knowledge of CAM modalities was generally rated as minimal or none by students. Among the 15 CAM modalities incorporated in the survey, massage, acupuncture, and meditation received the highest interest from students. Students who believe in a religion had a higher interest in CAM (p</p

In vitro and in vivo assessment of PEGylated PEI for anti-IL-8/CxCL-1 siRNA delivery to the lungs.

Inhalation offers a means of rapid, local delivery of siRNA to treat a range of autoimmune or inflammatory respiratory conditions. This work investigated the potential of a linear 10 kDa Poly(ethylene glycol) (PEG)-modified 25 kDa branched polyethyleneimine (PEI) (PEI-LPEG) to effectively deliver siRNA to airway epithelial cells. Following optimization with anti- glyceraldehyde 3-phosphate dehydrogenase (GAPDH) siRNA, PEI and PEI-LPEG anti-IL8 siRNA nanoparticles were assessed for efficacy using polarised Calu-3 human airway epithelial cells and a twin stage impinger (TSI) in vitro lung model. Studies were then advanced to an in vivo lipopolysaccharide (LPS)-stimulated rodent model of inflammation. In parallel, the suitability of the siRNA-loaded nanoparticles for nebulization using a vibrating mesh nebuliser was assessed. The siRNA nanoparticles were nebulised using an Aerogen® Pro vibrating mesh nebuliser and characterised for aerosol output, droplet size and fine particle fraction. Only PEI anti-IL8 siRNA nanoparticles were capable of significant levels of IL-8 knockdown in vitro in non-nebulised samples. However, on nebulization through a TSI, only PEI-PEG siRNA nanoparticles demonstrated significant decreases in gene and protein expression in polarised Calu-3 cells. In vivo, both anti-CXCL-1 (rat IL-8 homologue) nanoparticles demonstrated a decreased CXCL-1 gene expression in lung tissue, but this was non-significant. However, PEI anti-CXCL-1 siRNA-treated rats were found to have significantly less infiltrating macrophages in their bronchoalveolar lavage (BAL) fluid. Overall, the in vivo gene and protein inhibition findings indicated a result more reminiscent of the in vitro bolus delivery rather than the in vitro nebulization data. This work demonstrates the potential of nebulised PEI-PEG siRNA nanoparticles in modulating pulmonary inflammation and highlights the need to move towards more relevant in vitro and in vivo models for respiratory drug development

Investigation of the physical, chemical and microbiological stability of losartan potassium 5 mg/mL extemporaneous oral liquid suspension

Extemporaneous oral liquid preparations are commonly used when there is no commercially available dosage form for adjustable dosing. In most cases, there is a lack of stability data to allow for an accurately assigned shelf life and storage conditions to give greater confidence of product safety and efficacy over its shelf life. The aim of this study was to evaluate the physical, chemical and microbiological stability of an extemporaneous oral liquid suspension of losartan potassium, 5 mg/mL, used to treat paediatric hypertension in Our Lady's Children's Hospital Crumlin, Ireland. The losartan content of extemporaneous oral suspensions, prepared with and without addition of water, was measured by UV and confirmed by HPLC analysis. Suspensions were stored at 4 °C and room temperature (RT) and were monitored for changes in; pH, colour, odour, re-dispersibility, Total Aerobic Microbial Count, Total Yeast and Mould Count and absence of E. coli. Results showed that suspensions prepared by both methods, stored at 4 °C and RT, were physically and microbiologically stable over 28 days. Initial losartan content of all suspensions was lower than expected at 80-81% and did not change significantly over the 28 days. HPLC and NMR did not detect degradation of losartan in the samples. Suspensions prepared in water showed 100% losartan content. The reduced initial losartan content was confirmed by HPLC and was related to the acidic pH of the suspension vehicle. Physiochemical properties of the drug are important factors for consideration in the selection of suspension vehicle for extemporaneous compounding of oral suspensions as they can influence the quality, homogeneity and efficacy of these preparations

'Smart' non-viral delivery systems for targeted delivery of RNAi to the lungs.

The emergence of RNAi offers a potentially exciting new therapeutic paradigm for respiratory diseases. However, effective delivery remains a key requirement for their translation into the clinic and has been a major factor in the limited clinical success seen to date. Inhalation offers tissue-specific targeting of the RNAi to treat respiratory diseases and a diminished risk of off-target effects. In order to deliver RNAi directly to the respiratory tract via inhalation, 'smart' non-viral carriers are required to protect the RNAi during delivery/aerosolization and enhance cell-specific uptake to target cells. Here, we review the state-of-the-art in therapeutic aerosol bioengineering, and specifically non-viral siRNA delivery platforms, for delivery via inhalation. This includes developments in inhaler device engineering and particle engineering, including manufacturing methods and excipients used in therapeutic aerosol bioengineering that underpin the development of smart, cell type-specific delivery systems to target siRNA to respiratory epithelial cells and/or alveolar macrophages.</p

Synthesis and evaluation of novel 2,2-dimethylthiochromanones as anti-leishmanial agents

Within this work, we describe the design and synthesis of a range of novel thiochromanones based on natural products reported to possess anti-leishmanial action, and their synthetic derivatives. All compounds were elaborated via the key intermediate 2,2,6-trimethoxythiochromanone, which was modified at the benzylic position to afford various ester, amine and amide analogues, substituted by chains of varying lipophilicity. Upon testing in Leishmania, IC values revealed the most potent compounds to be phenylalkenyl and haloalkyl amides 11a and 11e, with IC values of 10.5 and 7.2 µM, respectively