High Antiproliferative Activity of Hydroxythiopyridones over Hydroxypyridones and Their Organoruthenium Complexes.

Hydroxypyr(id)ones are a pharmaceutically important class of compounds that have shown potential in diverse areas of drug discovery. We investigated the 3-hydroxy-4-pyridones 1a-1c and 3-hydroxy-4-thiopyridones 1d-1f as well as their Ru(η6-p-cymene)Cl complexes 2a-2f, and report here the molecular structures of 1b and 1d as determined by X-ray diffraction analysis. Detailed cell biological investigations revealed potent cytotoxic activity, in particular of the 3-hydroxy-4-thiopyridones 1d-1f, while the Ru complexes of both compound types were less potent, despite still showing antiproliferative activity in the low µM range. The compounds did not modulate the cell cycle distribution of cancer cells but were cytostatic in A549 and cytotoxic in NCI-H522 non-small lung cancer cells, among other effects on cancer cells.

Multimorbidity in Maori and Pacific patients: cross-sectional study in a Dunedin general practice.

INTRODUCTION Multimorbidity is a major issue in primary health care. AIM To determine the prevalence of multimorbidity and polypharmacy in one general practice in relation to age, sex and socioeconomic deprivation in Maori and Pacific patients. METHODS A cross-sectional study using data manually extracted from electronic medical records was conducted using a stratified random sample of Maori and Pacific patients aged ≥ 35 years who were enrolled with a large urban Dunedin general practice. The data were analysed to identify the number and type of morbidities, and prevalence of multimorbidity and polypharmacy in relation to age, sex and socioeconomic deprivation. RESULTS Half (52.5% [95% CI 44.5-60.4]) of Maori and 64.3% (95% CI 51.9-75.4) of Pacific patients had multimorbidity; 22.8% (95% CI 16.6-30.1) of Maori and 10.0% (95% CI 4.1-19.5) of Pacific patients had physical and mental health co-morbidity. Fewer (13.6% [95% CI 8.7-19.8]) Maori than Pacific patients (32.9% [95% CI 22.1-45.1]) had polypharmacy. The prevalence of multimorbidity in both Maori and Pacific patients increased with age and with increasing levels of socioeconomic deprivation. The eight most prevalent chronic conditions in both Maori and Pacific patients were obesity, anxiety or depression, hypertension, asthma or chronic obstructive pulmonary disease, gout, diabetes, cardiovascular disease and osteoarthritis. CONCLUSION The high prevalence of multimorbidity in Maori and Pacific patients requires the New Zealand health system to deliver culturally competent primary health care and to re-orientate health-care delivery around multimorbidity.