Discovery of Alkyl Triphenylphosphonium Pinostrobin Derivatives as Potent Anti-Breast Cancer Agents.

Pinostrobin demonstrated anticancer properties, but its hydrophobic feature led to a reduction in bioavailability. The mitochondria-targeted approach successfully synthesized eight new alkyl triphenylphosphonium pinostrobin derivatives (1-8) with good yield in this study. Seven compounds (1-3, 5-8) showed greater cytotoxic potency against the human MCF-7 breast cancer cell line than pinostrobin. Molecular docking studies were performed with two important targets in hormone-dependent anticancer strategies, estrogen receptor α (ERα) ligand binding domains, 3ERT (antagonist recognition and antiproliferative function), and 1GWR (agonist recognition and pro-proliferative function). In addition, the MD simulation study of the two most potent compounds (2 and 3) complexed with both ERα forms suggested that compounds 2 and 3 could serve as favourable antagonists. Furthermore, the in silico ADMET prediction indicated that compounds 2 and 3 could be potential drug candidates.

Unspecified opioids among opioid overdoses in Oslo, Norway.

OBJECTIVE: Since 2017, an increasing number of opioid overdoses in Oslo, Norway, has been categorized as involving unspecified opioids, as noted in the patient records by the doctor treating the patient. In this study we compare the characteristics of overdoses involving unspecified opioids, long-acting opioids, and heroin. Data on patients presenting with opioid overdose was retrospectively collected from 1 October 2013 to 31 December 2019 at the Oslo Accident and Emergency Outpatient Clinic. RESULTS: Among 2381 included cases, 459 (19.3%) involved unspecified opioids, 134 (5.6%) long-acting opioids, and 1788 (75.1%) heroin. Overdoses involving unspecified opioids needed longer observation, median 5 h 29 min vs. 4 h 54 min (long-acting opioids) and 4 h 49 min (heroin) (p < 0.001), and had a lower Glasgow coma scale score, median 10 vs. 13 in both the other groups (p < 0.001). Naloxone was given in 23.3% of cases involving unspecified opioids, vs. 12.7% involving long-acting opioids and 30.2% involving heroin (p < 0.001). A larger proportion of patients were transferred to hospital care when unspecified or long-acting opioids were involved compared to heroin, 16.3% and 18.7% respectively vs. 10.1% (p < 0.001). Our results indicate that the category "unspecified opioids" encompasses a substantial proportion of opioids acting longer than heroin.