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Alzheimer’s Disease (AD) is the most common form of dementia in individuals over the age of 65. There is no known prevention for the progression of the disease, although the FDA recently approved two drugs for AD. The exact etiology of AD is still under debate; however, it is commonly associated with the aggregation of amyloid-beta (Aβ) plaques in the brain. Recently some extended chalcones were reported to be potential anti-amyloidogenic agents. In this study, a larger library of extended chalcone analogs were synthesized with modifications on both rings. These were tested using the Thioflavin T fluorescence assay to measure their anti-Aβ aggregation properties. Three notably active compounds were further evaluated for potential neurotoxicity and neuroprotection using an MTT cell viability assay. These compounds were non-neurotoxic and displayed a trend toward neuroprotection. These were further assessed in a Drosophila melanogaster animal AD model. A forced climbing assay revealed statistically significant changes in flies’ movement by ~30% when fed these anti-amyloidogenic agents.

A novel class of platinum containing anticancer agents, specifically aza‑platinum-dipyrromethenes (aza-PLADIPYs) has been developed and assessed. These were synthesized with the aim of being dual-acting anticancer agents, hypothesized to produce both DNA crosslinking chemotoxicity and phototoxicity. The aza-PLADIPYs displayed a distorted square planar structure, which unexpectedly included a PtC bond. We compared the activity of these agents to that of Photofrin® (a photodynamic therapy (PDT) agent) and cisplatin (a DNA crosslinking agent). These compounds did not exhibit any PDT activity. However, they demonstrated promising cytotoxicity against partial cisplatin-resistant human ovarian carcinoma (OVCAR5) cells. Among the tested compounds, Compound 4 (R = OCH3) exhibited the highest cytotoxicity, achieving approximately 78 % cell death at 250 μM, which is significantly higher than the 54 % cell death observed with cisplatin at the same concentration. Impressively, the aza-PLADIPYs displayed virtually no nephrotoxicity at concentrations up to 250 μM, when tested on HK-2 kidney proximal tubule cells, overcoming one of the major dose-limiting side effects of platinum containing anticancer agents.

Currently, there is neither a cure for Alzheimer’s disease (AD) nor a way to stop the progressive death of neuronal cells associated with this devastating aliment. To date, there are only medications that temporarily slow its progression, and do not interfere with its pathogenesis. One of the hallmarks of AD is the presence of amyloid-beta plaques derived from the metabolism of the amyloid precursor protein, via the cleavage by beta followed by gamma secretase. Homotaurine, a naturally occurring small molecule found in some seaweeds, and curcumin, a phenolic antioxidant found in Curcuma longa, have been extensively studied as potential compounds to prevent/reverse plaque formation. In this study, libraries of chalcones and extended chalcones based on curcumin, as well as aminopropylsulfonamides inspired by homotaurine, were synthesized. Using fluorescence spectroscopic analysis with Thioflavin T, the anti-aggregation effect on Aβ42 was determined. A select number of newly synthesized chalcones and extended chalcone analogs were revealed to be potential anti-amyloidogenic agents. These were further evaluated with regard to their neurotoxicity/neuroprotection. The extended chalcone analogs that displayed the most anti-aggregation effect on Aβ42 were further analyzed in an MTT assay. Although none of the compounds alone displayed any neurotoxicity, none were able to provide neuroprotection against Aβ42.

Abstract Background Delirium is more prevalent in older people and estimated to occur in up to 50% of the hospital population. Delirium comprises a spectrum of behaviours, including cognitive and attention deficits, and fluctuating levels of consciousness, often associated with an underlying physiological disturbance. Delirium has been increasingly associated with adverse outcomes. Although often preventable or can at least be mitigated, delirium may not be a standard part of assessment and thus may not be recognized in the early stages when it is most likely to be treated successfully. The aim of this study was to evaluate the level of knowledge of delirium amongst clinicians caring for patients at high risk of developing delirium and to determine whether education can improve clinical assessment of delirium. Methods Two hundred and forty-six case notes were audited before and 149 were reviewed after the education intervention and implementation of a delirium screening tool. Clinicians at the hospital were invited to complete a questionnaire on knowledge of delirium. The questionnaire was based on a validated tool which contained 39 questions about delirium. The questionnaire also contained 28 questions on delirium knowledge. Additional questions were included to gather demographic information specific to the hospital. Descriptive statistics, chi square and independent t-tests were conducted to test for differences in knowledge between the pre and post periods. The Squire Checklist Reporting Guidelines for Quality Improvement Studies informed the preparation of the manuscript. Results The audit demonstrated that the use of a cognitive assessment tool overall increased from 8.5% in pre education to 43% in the post education period. One hundred and fifty-nine staff completed the questionnaire in total, 118 the pre and 41 post. The knowledge subscale score was high pre and post education and no statistically significant difference was observed. The greatest increase in knowledge was related to knowledge of the risk factors subscale. The increase in knowledge (6.8%) was statistically significant. Conclusion An interprofessional approach to delirium education was effective in not only increasing awareness of the factors associated with this syndrome but also increased the use of a delirium assessment tool.