Oseltamivir phosphonic acid (tamiphosphor, 3a), its monoethyl ester (3c), guanidino-tamiphosphor (4a) and its monoethyl ester (4c) are potent inhibitors of influenza neuraminidases. They inhibit the replication of influenza viruses, including the oseltamivir-resistant H275Y strain, at low nM to pM levels, and significantly protect mice from infection with lethal doses of influenza viruses when orally administered with 1 mg/kg or higher doses. These compounds are stable in simulated gastric fluid, liver microsomes and human blood, and are largely free from binding to plasma proteins. Pharmacokinetic properties of these inhibitors are thoroughly studied in dogs, rats and mice. The absolute oral bioavailability of these compounds was lower than 12%. No conversion of monoester 4c to phosphonic acid 4a was observed in rats after intravenous administration, but partial conversion of 4c was observed with oral administration. Advanced formulation may be investigated to develop these new anti-influenza agents for better therapeutic use.

Acute lymphoblastic leukemia (ALL) is a common hematological malignancy characterized by the uncontrolled proliferation of leukemia cells in children. Discovering and developing effective chemotherapeutic drugs are needed for ALL. In this study, we investigated the anti-leukemic activity of butein and its action mechanisms in ALL. Butein was found to significantly suppress the cellular proliferation of ALL cell lines and primary ALL blasts in a dose-dependent manner. It also induced cell cycle arrest by decreasing the expression of cyclin E and CDK2. We also found that butein promoted nuclear Forkhead Class box O3a (FOXO3a) localization, enhanced the binding of FOXO3a on the p27kip1 gene promoter and then increased the expression of p27kip1. Moreover, we showed that FOXO3a knockdown significantly decreased the proliferation inhibition by butein, whereas overexpression of FOXO3a enhanced the butein-mediated proliferation inhibition. However, overexpression of FOXO3a mutation (C-terminally truncated FOXO3a DNA-binding domain) decreased the proliferation inhibition by butein through decreasing the expression of p27kip1. Our results therefore demonstrate the therapeutic potential of butein for ALL via FOXO3a/p27kip1 pathway.

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Mn–Zn ferrite powders were prepared by hydrothermally aging the coprecipitates of compositional metal ions using ammonium hydroxide as a precipitant. R value (alkalinity) = (moles of added OH−)/[(moles of added Zn2+) × 2 + (moles of added Mn2+) × 2 + (moles of added Fe3+) × 3] was introduced to adjust the amount of added ammonia. The results show that the R value of starting suspension and hydrothermal time have similar and dominant effects on the composition, spinel ratio, and crystallite size of synthesized powders. From the analyses of x-ray diffraction (XRD) and inductively-coupled plasma (ICP), it notes that no α–Fe2O3 peak in the XRD patterns of powders synthesized at R = 2–3, 150 °C × 2 h, may be due to lower degree of crystallinity and less amount of α–Fe2O3 existing in these powders. Both the increase of hydrothermal time and of R value can promote the crystallinity of powders and also cause a significant loss of zinc, hinting that in the hydrothermal process, the loss of zinc may play a crucial role in the crystallinity of hydrothermally synthesized powders.

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