Effect of selected silyl groups on the anticancer activity of 3,4-dibromo-5-hydroxy-furan-2(5H)-one derivatives

The pharmacological effects of carbon to silicon bioisosteric replacements have been widely explored in drug design and medicinal chemistry. Here, we present a systematic investigation of the impact of different silyl groups on the anticancer activity of mucobromic acid (MBA) bearing furan-2(5H)-one core. We describe a comprehensive characterization of obtained compounds with respect to their anticancer potency and selectivity towards cancer cells. All four novel compounds exert stronger antiproliferative activity than MBA. Moreover, 3b induce apoptosis in colon cancer cell lines. A detailed investigation of the mechanism of action revealed that 3b activity stems from the down-regulation of survivin and the activation of caspase-3. Furthermore, compound 3b attenuates the clonogenic potential of HCT-116 cells. Interestingly, we also found that depending on the type of the silyl group, compound selectivity towards cancer cells could be precisely controlled. Collectively, we demonstrated the utility of silyl groups for adjusting both the potency and selectivity of silicon-containing compounds. These data reveal a link between the types of silyl group and compound potency, which could have bearings for the design of novel silicon-based anticancer drugs

Usporedba izolacijskih svojstava vune alpaka (Huacayo alpaca) i merino ovaca

The aim of the study was to evaluate and compare the fleece thermal insulation of Huacaya alpacas and Merino sheep. The study included 13 clinically healthy Huacaya alpacas and 14 Merino sheep. Fleece samples were taken from the trunk (lateral aspects) of each animal to measure coat fibre length and average fibre diameter. The insulating properties of each sample were determined using a calorimetric method. In addition, infrared thermographic images were taken of the trunk (lateral aspects) for both species in an indoor environment. Four regions of interest (ROIs) were determined from each thermographic image (corresponding to the coat sample sites) and the mean temperature within each ROI was calculated. Merino sheep had significantly (P<0.001) longer and thicker fibres than alpacas, but less efficient (by about 20%) insulation at all sample sites. Sheep in similar experimental conditions therefore had significantly higher fleece surface temperature (by 1 - 2 °C) than Huacaya alpacas. Infrared thermography also provides information about fleece surface temperatures in vivo, which can be used to validate models of heat exchange in homeotherms.Cilj ovoga istraživanja jest procjena i usporedba vune alpaka (Huacayo alpaca) i merino ovaca kao toplinskog izolatora. Istraživanje je obuhvatilo 13 klinički zdravih alpaka i 14 merino ovaca. Uzorci vune uzeti su s lateralnog dijela trupa svake životinje kako bi se izmjerili dužina i promjer vlakana. Izolacijska svojstva svakoga uzorka određena su kalorimetrijskom metodom. Također su učinjene infracrvene termografske snimke lateralnog dijela trupa s kojega su uzeti uzorci u obje skupine u zatvorenom prostoru. Na svakoj su snimci određene četiri regije (na temelju mjesta uzorkovanja) te je izračunata prosječna temperatura. Vuna merino ovaca imala je znakovito duža i deblja vlakna od vune alpaka (P<0,001), ali manje učinkovitu izolaciju (oko 20 %) u svim uzorcima. Ovce u sličnim pokusnim uvjetima imale su znakovito višu temperaturu površine vune (1-2 ⁰C) od alpaka. Infracrvena termografija pruža podatke i o temperaturi površine vlakana in vivo, što se može upotrijebiti za vrednovanje modela u izmjeni temperature toplokrvnih životinja

Highly pathogenic avian influenza H5N8 in Poland in 2019–2020

Repeated incursions of highly pathogenic avian influenza virus (HPAIV) H5 subtype of Gs/GD lineage pose a serious threat to poultry worldwide. We provide a detailed analysis of the spatio-temporal spread and genetic characteristics of HPAIV Gs/GD H5N8 from the 2019/20 epidemic in Poland

Glycoconjugates of Mucochloric Acid—Synthesis and Biological Activity

The pharmacological effects of the presence of a sugar moiety, 1,2,3-triazole ring and silyl groups in the structure of biologically active compounds have been extensively studied in drug design and medicinal chemistry. These components can be useful tools to tailoring the bioavailability of target molecules. Herein we present the study on the impact of the sugar substituent structure and triisopropylsilyl group presence on the anticancer activity of mucochloric acid (MCA) derivatives containing the furan-2(5H)-one or 2H-pyrrol-2-one core. The obtained results clearly indicated that tested compounds caused a significant decrease in cell viability of HCT116 and MCF-7 cell lines. MCF-7 cells indicate serious resistance toward investigated compounds in comparison with HCT116 cell line, it suggests that estrogen-dependent breast cancer cells are significantly less sensitive to the tested derivatives. Depending on the structure of the sugar, the type and site of connection with the furanone or 2H-pyrrol-2-one derivative and the presence of the silyl group, the selectivity of the compound towards cancer cells can be controlled. The obtained results may have an impact on the design of new furanone-based anticancer compounds