6-Acetyl-5-hydroxy-4,7-dimethylcoumarin derivatives : design, synthesis, modeling studies, 5-HT1A, 5-HT2A and D2 receptors affinity

Molecular docking studies using appropriate 5-HT$_{1A}$, 5-HT$_{2A}$ and D$_{2}$ receptors models were used to design sixteen new 5-hydroxycoumarin derivatives with piperazine moiety (3–18). The microwave radiation have been used to synthesize them and their structures have been confirmed using mass spectrometry, $^{1}$H and $^{13}$C NMR. All newly prepared derivatives were evaluated for their 5-HT$_{1A}$, 5-HT$_{2A}$ and D$_{2}$ receptor affinity. Seven of the synthesized derivatives showed very high affinities to 5-HT$_{1A}$ receptor (3–4.0 nM, 6–4.0 nM, 7–1.0 nM, 9–6.0 nM, 15–4.3 nM, 16–1.0 nM, 18–3.0 nM) and one of them showed high affinities to 5-HT$_{2A}$ receptor (16–8.0 nM). In the case of the D$_{2}$ receptor none of the tested derivatives showed high affinity. Compounds 7 and 16 were identified as potent antagonists of the 5-HT$_{1A}$ receptor as shown by the [35S]GTPcS binding assay but they didn’t show any antidepressant effect at the single dose tested (10 mg/kg) in the tail suspension tests

Evaluation of the Effectiveness of the National Clean Air Programme in Terms of Health Impacts from Exposure to PM2.5 and NO2 Concentrations in Poland

The health impact of air quality has recently become an emerging issue. Many regions, especially densely populated regions, have deteriorating air quality. The primary source of pollution in Poland is the municipal sector. Air pollutants have a negative impact on human health, contribute to premature deaths, and are the cause of various diseases. Over recent years, Europe’s air quality has largely improved due to several measures to reduce pollutant emissions. The following paper presents the impact of annual average PM2.5 and NO2 concentrations on premature deaths in Poland in 2019. Exposure to PM2.5 caused more than 19 000 premature deaths, and exposure to NO2 contributed to around 6000 premature deaths in 2019. Taking 2019 as a baseline, the impact of the envisaged implementation of the national Clean Air Programme on the number of premature deaths is analysed. Implementing the mitigation measures focused on replacing inefficient stoves and boilers in individual households would significantly improve air quality, mainly particulate matter. Reducing PM2.5 concentrations would reduce premature deaths by around 3000 cases, while for NO2, the number of premature deaths would not change much